JAK3 inhibitor administration in vivo in chronically SIV Infected Rhesus Macaques

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "JAK3 inhibitor administration in vivo in chronically SIV Infected Rhesus Macaques"

Transcription

1 JAK3 inhibitor administration in vivo in chronically SIV Infected Rhesus Macaques preferentially depletes NK Cells Ladawan Kowawisatsut 1 Kovit Pattanapanyasat 1 Aftab A. Ansari 2 1 Department of Immunology Faculty of Medicine Siriraj Hospital Mahidol University Thailand 1 Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand 2 Department of Pathology and Experimental Medicine, Emory University, USA

2 Why study NK-17 cells in the GALT? GALT is the one of the largest lymphocyte y storage site and also the primary site of HIV/SIV replication during acute infection NK cells are important innate cells in anti-viral immunity NK cells in Toxoplasmagondii-infected mice can produce IL-17 in the presence of IL-6, IL-23 and TGF- (The Journal of Immunology 2010,184: ) 184: ) IL-17 producing Th cells (Th17) have been reported as the important cells in protection of intestinal epithelial integrity and microbial translocation during SIV infection

3 JAK3 inhibitor Inhibits the common gamma chain cytokine pathways such as the IL-2, IL-7 and IL-15 signaling pathway Immunosuppressive agents that has been used in the clinic for the prevention of organ transplant rejection and autoimmune diseases Oral administration of the JAK3 inhibitor in cynomolgus monkey reduced the number of NK cells and CD8+ T cell which returned to baseline levels within 3 weeks following treatment cessation (Journal of Leukocyte Biology 2004;76: )

4 Pharmacokinetics of JAK3 inhibitor Groups of two rhesus macaques were administered 1, 5, 10, or 25 mg/kg JAK3 inhibitor orally and detailed safety and PK studies performed. At a dose of 10 mg/kg/day, sufficient drug trough levels were obtained that led to the preferential depletion of NK cells Dose was tolerated well with no clinical, metabolic, hematologic, renal/liver toxicity.

5 Aim of the study To determine the effects of in vivo NK cell depletion on viral loads and immune responses using a JAK3 inhibitor in chronically SIV infected rhesus macaques

6 Protocol Blood and Rectal biopsy from 6 intravenously SIVmac251- infected Rhesus macaques JAK3 inhibitor 10 mg/kg/day g for 35 days per os pre weeks Peripheral blood & colorectal biopsy collection to determine frequency of total and IL-17 NK cells Plasma monitored for drug levels PBMC analyzed for levels of phosphorylated STAT-5

7 Methods Mononuclear cells from blood and rectal biopsy py Stimulate with 25 ng/ml PMA and 1 mg/ml Ionomycin Add 0.5 mg/ml Brefeldin A Overnight stimulation Cell surface and Intracellular cytokine staining FITC PE PerCP-Cy5 Cy5.55 PE-Cy7 APC Alexa700 PacBlue CD8 NKG2A CD16 CD56 IL-17 CD3 Live/Dead Flow cytometry analysis by LSRII

8 JAK3 inhibitor had modest effects on the frequencies of CD4 and CD8 T cells in PBMC and rectal biopsies * JAK 3 inhibitor CD4 T cells JAK 3 inhibitor CD8 T cells

9 JAK-3 inhibitor depleted NK cells in PBMC and rectal biopsy * JAK 3 inhibitor After cessation NK cells returned in PBMC, but not in rectal biopsy

10 JAK3 inhibitor also effects NK-17 cells in PBMC and rectal biopsy * * JAK 3 inhibitor PBMC JAK 3 inhibitor Rectal biopsy

11 Viral Loads in SIVmac251 chronically infected Rhesus Macaques administered JAK3 inhibitor copies/ml JAK 3 inhibitor Transient increase in viremia during JAK-3 inhibitor admin.

12 Viral Loads in SIVmac251 chronically infected Rhesus Macaques administered JAK3 inhibitor copies/ml JAK 3 inhibitor Transient increase of viremia during JAK3 inhibitor admin.

13 Conclusion The in vivo administration of a JAK3 inhibitor to chronically SIVmac251 infected monkeys depletes both total and NK-17 cells in the blood and mucosal tissue and is associated with a transient increases in viremia denoting an important role for NK cells during chronic SIV infection.

14 Acknowledgement Department of Pathology and Experimental Medicine Emory University School of Medicine Professor Aftab AA A.Ansari Ann Mayne Yoshi Takahashi Dawn Little Yerkes National Primate Research Center Emory University Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University Professor Kovit Pattanapanyasat The Royal Golden Jubilee Ph.D. Program, The Thailand Research Fund Grant from NIAID, NIH to Prof. A. Ansari

15 * * Mean ±SD PBMC Rectum Pre CP 4.80± ±0.88 Week ± ±4.98 Week ± ±1.19 Week ± ±0.62 Week ± ±0.64 Week ± ±0.70

In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection

In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection Yoshiaki Takahashi, Emory University Siddappa N. Byrareddy, Emory

More information

Loss of Effector and Anti-Inflammatory Natural Killer T Lymphocyte Function in Pathogenic Simian Immunodeficiency Virus Infection

Loss of Effector and Anti-Inflammatory Natural Killer T Lymphocyte Function in Pathogenic Simian Immunodeficiency Virus Infection Loss of Effector and Anti-Inflammatory Natural Killer T Lymphocyte Function in Pathogenic Simian Immunodeficiency Virus Infection Namita Rout, Harvard University Justin Greene, University of Wisconsin-Madison

More information

Optimizing Intracellular Flow Cytometry

Optimizing Intracellular Flow Cytometry Optimizing Intracellular Flow Cytometry Detection of Cytokines, Transcription Factors, and Phosphoprotein by Flow Cytometry Presented by Erika O Donnell, PhD, BD Biosciences 23-14876-00 Outline Basic principles

More information

Combined IL-21 and IFNα treatment limits inflammation and delay viral rebound in ART-treated, SIV-infected macaques

Combined IL-21 and IFNα treatment limits inflammation and delay viral rebound in ART-treated, SIV-infected macaques Combined and IFNα treatment limits inflammation and delay viral rebound in ART-treated, SIV-infected macaques Mirko Paiardini Associate Professor, Emory University School of Medicine Yerkes National Primate

More information

David Verhoeven, Sumathi Sankaran, Melanie Silvey, and Satya Dandekar*

David Verhoeven, Sumathi Sankaran, Melanie Silvey, and Satya Dandekar* JOURNAL OF VIROLOGY, Apr. 2008, p. 4016 4027 Vol. 82, No. 8 0022-538X/08/$08.00 0 doi:10.1128/jvi.02164-07 Copyright 2008, American Society for Microbiology. All Rights Reserved. Antiviral Therapy during

More information

Optimizing Intracellular Flow Cytometry:

Optimizing Intracellular Flow Cytometry: Optimizing Intracellular Flow Cytometry: Simultaneous Detection of Cytokines and Transcription Factors Presented by Jurg Rohrer, PhD, BD Biosciences 23-10780-00 Outline Introduction Cytokines Transcription

More information

Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques

Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques Luca Micci, Emory University Emily S. Ryan, Emory University Rémi Fromentin, Université de Montréal Steven

More information

DEBATE ON HIV ENVELOPE AS A T CELL IMMUNOGEN HAS BEEN GAG-GED

DEBATE ON HIV ENVELOPE AS A T CELL IMMUNOGEN HAS BEEN GAG-GED DEBATE ON HIV ENVELOPE AS A T CELL IMMUNOGEN HAS BEEN GAG-GED Viv Peut Kent Laboratory, University of Melbourne, Australia WHY ENVELOPE? Env subject to both humoral and cellular immune responses Perhaps

More information

EBV Infection and Immunity. Andrew Hislop Institute for Cancer Studies University of Birmingham

EBV Infection and Immunity. Andrew Hislop Institute for Cancer Studies University of Birmingham EBV Infection and Immunity Andrew Hislop Institute for Cancer Studies University of Birmingham EBV Introduction Large ds DNA virus Spread by saliva contact Lifelong infection Predominantly B-lymphotropic

More information

PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques

PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques Brief report Related Commentary, page 1611 PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques Ravi Dyavar Shetty, 1 Vijayakumar Velu,

More information

Re-Evaluation of PD-1 Expression by T Cells as a Marker for Immune Exhaustion during SIV Infection

Re-Evaluation of PD-1 Expression by T Cells as a Marker for Immune Exhaustion during SIV Infection Re-Evaluation of PD-1 Expression by T Cells as a Marker for Immune Exhaustion during SIV Infection Jung Joo Hong, Emory University Praveen K Amancha, Emory University Kenneth Rogers, Emory University Aftab

More information

Supplemental Information. T Cells Enhance Autoimmunity by Restraining Regulatory T Cell Responses via an Interleukin-23-Dependent Mechanism

Supplemental Information. T Cells Enhance Autoimmunity by Restraining Regulatory T Cell Responses via an Interleukin-23-Dependent Mechanism Immunity, Volume 33 Supplemental Information T Cells Enhance Autoimmunity by Restraining Regulatory T Cell Responses via an Interleukin-23-Dependent Mechanism Franziska Petermann, Veit Rothhammer, Malte

More information

Supplementary Figure 1. ETBF activate Stat3 in B6 and Min mice colons

Supplementary Figure 1. ETBF activate Stat3 in B6 and Min mice colons Supplementary Figure 1 ETBF activate Stat3 in B6 and Min mice colons a pstat3 controls Pos Neg ETBF 1 2 3 4 b pstat1 pstat2 pstat3 pstat4 pstat5 pstat6 Actin Figure Legend: (a) ETBF induce predominantly

More information

Increased Loss of CCR5 CD45RA CD4 T Cells in CD8 Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Increased Loss of CCR5 CD45RA CD4 T Cells in CD8 Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys JOURNAL OF VIROLOGY, June 2008, p. 5618 5630 Vol. 82, No. 11 0022-538X/08/$08.00 0 doi:10.1128/jvi.02748-07 Copyright 2008, American Society for Microbiology. All Rights Reserved. Increased Loss of CCR5

More information

BEAT-HIV Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy

BEAT-HIV Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy BEAT-HIV Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy We are pleased to announce that the National Institutes of Health (NIH) has awarded nearly $23 million to co-principal

More information

SUPPORTING INFORMATIONS

SUPPORTING INFORMATIONS SUPPORTING INFORMATIONS Mice MT/ret RetCD3ε KO α-cd25 treated MT/ret Age 1 month 3 mnths 6 months 1 month 3 months 6 months 1 month 3 months 6 months 2/87 Survival 87/87 incidence of 17/87 1 ary tumor

More information

NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2009 July 1.

NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2009 July 1. NIH Public Access Author Manuscript Published in final edited form as: Nature. 2009 January 1; 457(7225): 87 91. doi:10.1038/nature07469. Immune Control of an SIV Challenge by a T Cell-Based Vaccine in

More information

Supplementary Figure 1. Example of gating strategy

Supplementary Figure 1. Example of gating strategy Supplementary Figure 1. Example of gating strategy Legend Supplementary Figure 1: First, gating is performed to include only single cells (singlets) (A) and CD3+ cells (B). After gating on the lymphocyte

More information

CROI 2016 Review: Immunology and Vaccines

CROI 2016 Review: Immunology and Vaccines Frontier AIDS Education and Training Center CROI 2016 Review: Immunology and Vaccines Meena Ramchandani MD MPH Acting Instructor, University of Washington March 2016 This presentation is intended for educational

More information

DEFINING DENDRITIC CELLS AND MACROPHAGES IN LYMPH NODES AND GUT MUCOSA DURING SIMIAN IMMUNODEFICIENCY VIRUS INFECTION. Zachary Duane Jameson Swan

DEFINING DENDRITIC CELLS AND MACROPHAGES IN LYMPH NODES AND GUT MUCOSA DURING SIMIAN IMMUNODEFICIENCY VIRUS INFECTION. Zachary Duane Jameson Swan DEFINING DENDRITIC CELLS AND MACROPHAGES IN LYMPH NODES AND GUT MUCOSA DURING SIMIAN IMMUNODEFICIENCY VIRUS INFECTION by Zachary Duane Jameson Swan B.S., University of North Carolina at Chapel Hill, 2006

More information

Recommended Protocols for Phospho Protein Detection in Human Cells

Recommended Protocols for Phospho Protein Detection in Human Cells Recommended Protocols for Phospho Protein Detection in Human Cells Depending on subcellular localization of the phospho protein of interest, as well as epitope susceptibility to cell fixing and permeabilizing

More information

Medical Virology Immunology. Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University

Medical Virology Immunology. Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University Medical Virology Immunology Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University Human blood cells Phases of immune responses Microbe Naïve

More information

Combination antiretroviral therapy (ART) has. Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure

Combination antiretroviral therapy (ART) has. Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 33, Number S1, 2017 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2017.0153 Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure Shahzada

More information

Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options

Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options Velu et al. Retrovirology (2015) 12:14 DOI 10.1186/s12977-015-0144-x REVIEW Open Access Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options Vijayakumar Velu 1,2*, Ravi

More information

Chapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally!

Chapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally! MCMP422 Immunology and Biologics Immunology is important personally and professionally! Learn the language - use the glossary and index RNR - Reading, Note taking, Reviewing All materials in Chapters 1-3

More information

Scott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION

Scott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION Scott Abrams, Ph.D. Professor of Oncology, x4375 scott.abrams@roswellpark.org Kuby Immunology SEVENTH EDITION CHAPTER 11 T-Cell Activation, Differentiation, and Memory Copyright 2013 by W. H. Freeman and

More information

Scott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION

Scott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION Scott Abrams, Ph.D. Professor of Oncology, x4375 scott.abrams@roswellpark.org Kuby Immunology SEVENTH EDITION CHAPTER 11 T-Cell Activation, Differentiation, and Memory Copyright 2013 by W. H. Freeman and

More information

Effector T Cells and

Effector T Cells and 1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New

More information

HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case cohort analysis

HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case cohort analysis HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case cohort analysis M Juliana McElrath, Stephen C De Rosa, Zoe Moodie, Sheri Dubey, Lisa Kierstead, Holly Janes, Olivier D Defawe, Donald

More information

Technical Resources. BD Immunocytometry Systems. FastImmune Intracellular Cytokine Staining Procedures

Technical Resources. BD Immunocytometry Systems. FastImmune Intracellular Cytokine Staining Procedures FastImmune Intracellular Cytokine Staining Procedures BD has developed protocols for the detection of intracellular cytokines in activated lymphocytes and in activated monocytes. The procedures have been

More information

HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis

HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis Mireille Laforge 1., Laure Campillo-Gimenez 1., Valérie Monceaux 2, Marie-Christine Cumont 2, Bruno Hurtrel 2, Jacques Corbeil 3, John

More information

Supplemental Information. The Therapeutic Effect. of Anti-HER2/neu Antibody Depends. on Both Innate and Adaptive Immunity CONTENTS:

Supplemental Information. The Therapeutic Effect. of Anti-HER2/neu Antibody Depends. on Both Innate and Adaptive Immunity CONTENTS: Cancer Cell, Volume 18 Supplemental Information The Therapeutic Effect of Anti-HER2/neu Antibody Depends on Both Innate and Adaptive Immunity SaeGwang Park, Zhujun Jiang, Eric D. Mortenson, Liufu Deng,

More information

Hua Tang, Weiping Cao, Sudhir Pai Kasturi, Rajesh Ravindran, Helder I Nakaya, Kousik

Hua Tang, Weiping Cao, Sudhir Pai Kasturi, Rajesh Ravindran, Helder I Nakaya, Kousik SUPPLEMENTARY FIGURES 1-19 T H 2 response to cysteine-proteases requires dendritic cell-basophil cooperation via ROS mediated signaling Hua Tang, Weiping Cao, Sudhir Pai Kasturi, Rajesh Ravindran, Helder

More information

From Bench to Bedside Regulatory T Cells: Can We Make the Police Work for Us?

From Bench to Bedside Regulatory T Cells: Can We Make the Police Work for Us? From Bench to Bedside Regulatory T Cells: Can We Make the Police Work for Us? Sang Mo Kang, MD Qizhi Tang, PhD UCSF Division of Transplantation UCSF Transplant Conference 2012 The Reality of Immunosuppression

More information

Supplementary Figures. Supplementary Figure 1. Treatment schematic of SIV infection and ARV and PP therapies.

Supplementary Figures. Supplementary Figure 1. Treatment schematic of SIV infection and ARV and PP therapies. Supplementary Figures Supplementary Figure 1. Treatment schematic of SIV infection and ARV and PP therapies. Supplementary Figure 2. SIV replication and CD4 + T cell count. (A) Log SIVmac239 copies/ml

More information

Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection

Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection Kevin N. Brown 1,2, Viskam Wijewardana 2, Xiangdong Liu 2, Simon

More information

Received 19 September 2007/Accepted 21 November 2007

Received 19 September 2007/Accepted 21 November 2007 JOURNAL OF VIROLOGY, Feb. 2008, p. 1723 1738 Vol. 82, No. 4 0022-538X/08/$08.00 0 doi:10.1128/jvi.02084-07 Copyright 2008, American Society for Microbiology. All Rights Reserved. Patterns of CD8 Immunodominance

More information

Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells

Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells Andrew H. Lichtman, M.D. Ph.D. Department of Pathology Brigham and Women s Hospital and Harvard

More information

SIMIAN IMMUNODEFICIENCY VIRUS PATHOGENESIS AND THE GASTROINTESTINAL TRACT. Jessica Malzahn. B.S., University of Wisconsin La Crosse, 2005

SIMIAN IMMUNODEFICIENCY VIRUS PATHOGENESIS AND THE GASTROINTESTINAL TRACT. Jessica Malzahn. B.S., University of Wisconsin La Crosse, 2005 SIMIAN IMMUNODEFICIENCY VIRUS PATHOGENESIS AND THE GASTROINTESTINAL TRACT by Jessica Malzahn B.S., University of Wisconsin La Crosse, 2005 Submitted to the Graduate Faculty of the Graduate School of Public

More information

CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells

CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells Luca Micci, Emory University Xavier Alvarez, Tulane University Robin I. Iriele,

More information

Blocking antibodies and peptides. Rat anti-mouse PD-1 (29F.1A12, rat IgG2a, k), PD-

Blocking antibodies and peptides. Rat anti-mouse PD-1 (29F.1A12, rat IgG2a, k), PD- Supplementary Methods Blocking antibodies and peptides. Rat anti-mouse PD-1 (29F.1A12, rat IgG2a, k), PD- L1 (10F.9G2, rat IgG2b, k), and PD-L2 (3.2, mouse IgG1) have been described (24). Anti-CTLA-4 (clone

More information

20 ml (1 ea) 40 ml (1 ea) 25 ml (1 ea) 7.5 ml (1 ea)

20 ml (1 ea) 40 ml (1 ea) 25 ml (1 ea) 7.5 ml (1 ea) Technical Data Sheet Transcription Factor Phospho Buffer Set Product Information Material Number: 565575 25 Tests Component: 51-9011474 Description: 0.75X TFP Diluent Buffer 20 ml (1 ea) BD Pharmingen

More information

Felix Yarovinsky. Department of Immunology, UT Southwestern Medical Center. Innate immune defense to Toxoplasma gondii

Felix Yarovinsky. Department of Immunology, UT Southwestern Medical Center. Innate immune defense to Toxoplasma gondii Felix Yarovinsky Department of Immunology, UT Southwestern Medical Center Innate immune defense to Toxoplasma gondii Pathogen recognition by innate immune cells Pathogen Parasites Viruses Bacteria Initiator

More information

Horizon 2020 Programme. SFS-01b Tackling losses from terrestrial animal diseases

Horizon 2020 Programme. SFS-01b Tackling losses from terrestrial animal diseases Horizon 2020 Programme SFS-01b-2014 Tackling losses from terrestrial animal diseases Strengthening Animal Production and Health through the Immune Response Project ID: 633184 D12.1 Age related innate responses

More information

Supplementary Figures

Supplementary Figures Supplementary Figures Supplementary Figure 1. NKT ligand-loaded tumour antigen-presenting B cell- and monocyte-based vaccine induces NKT, NK and CD8 T cell responses. (A) The cytokine profiles of liver

More information

Fluorochrome Panel 1 Panel 2 Panel 3 Panel 4 Panel 5 CTLA-4 CTLA-4 CD15 CD3 FITC. Bio) PD-1 (MIH4, BD) ICOS (C398.4A, Biolegend) PD-L1 (MIH1, BD)

Fluorochrome Panel 1 Panel 2 Panel 3 Panel 4 Panel 5 CTLA-4 CTLA-4 CD15 CD3 FITC. Bio) PD-1 (MIH4, BD) ICOS (C398.4A, Biolegend) PD-L1 (MIH1, BD) Additional file : Table S. Antibodies used for panel stain to identify peripheral immune cell subsets. Panel : PD- signaling; Panel : CD + T cells, CD + T cells, B cells; Panel : Tregs; Panel :, -T, cdc,

More information

CD40L-Adjuvanted DNA/MVA SIV Vaccine Enhances Protection. Against Neutralization Resistant Mucosal SIV Infection

CD40L-Adjuvanted DNA/MVA SIV Vaccine Enhances Protection. Against Neutralization Resistant Mucosal SIV Infection JVI Accepted Manuscript Posted Online 4 February 2015 J. Virol. doi:10.1128/jvi.03527-14 Copyright 2015, American Society for Microbiology. All Rights Reserved. 1 2 CD40L-Adjuvanted DNA/MVA SIV Vaccine

More information

Chitin Activates Parallel Immune Modules that Direct Distinct Inflammatory Responses via Innate Lymphoid Type 2 and T Cells

Chitin Activates Parallel Immune Modules that Direct Distinct Inflammatory Responses via Innate Lymphoid Type 2 and T Cells Immunity, Volume 4 Supplemental Information Chitin Activates Parallel Immune Modules that Direct Distinct Inflammatory Responses via Innate Lymphoid Type 2 and T Cells Steven J. Van Dyken, Alexander Mohapatra,

More information

Immunology Lecture 4. Clinical Relevance of the Immune System

Immunology Lecture 4. Clinical Relevance of the Immune System Immunology Lecture 4 The Well Patient: How innate and adaptive immune responses maintain health - 13, pg 169-181, 191-195. Immune Deficiency - 15 Autoimmunity - 16 Transplantation - 17, pg 260-270 Tumor

More information

Scott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION

Scott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION Scott Abrams, Ph.D. Professor of Oncology, x4375 scott.abrams@roswellpark.org Kuby Immunology SEVENTH EDITION CHAPTER 13 Effector Responses: Cell- and Antibody-Mediated Immunity Copyright 2013 by W. H.

More information

Massive infection and loss of memory CD4 + T cells in multiple tissues during acute SIV infection

Massive infection and loss of memory CD4 + T cells in multiple tissues during acute SIV infection Massive infection and loss of memory CD4 + T cells in multiple tissues during acute SIV infection Joseph J. Mattapallil 1, Daniel C. Douek 2, Brenna Hill 2, Yoshiaki Nishimura 3, Malcolm Martin 3 & Mario

More information

Simultaneous correlation of cytokine production with Treg and Th17 cell proliferation

Simultaneous correlation of cytokine production with Treg and Th17 cell proliferation Simultaneous correlation of cytokine production with Treg and Th17 cell proliferation Jurg Rohrer, PhD Director, R&D BD Biosciences 23-11773-00 For Research Use Only. Not for use in diagnostic or therapeutic

More information

Immunology The innate and adaptive immune systems

Immunology The innate and adaptive immune systems Immunology The innate and adaptive immune systems The immune system is the collection of cells, tissues and molecules that protects the body from numerous pathogenic microbes and toxins in our environment.

More information

Pathophysiologic Basis of Autoimmune Disorders

Pathophysiologic Basis of Autoimmune Disorders Pathophysiologic Basis of Autoimmune Disorders Linda Felver, Ph.D., R.N. Associate Professor School of Nursing Oregon Health & Science University The immune system has two arms: Adaptive (Acquired) Immune

More information

Van Rompay et al. Retrovirology 2012, 9:57

Van Rompay et al. Retrovirology 2012, 9:57 Van Rompay et al. Retrovirology 2012, 9:57 RESEARCH Open Access Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral

More information

Central tolerance. Mechanisms of Immune Tolerance. Regulation of the T cell response

Central tolerance. Mechanisms of Immune Tolerance. Regulation of the T cell response Immunoregulation: A balance between activation and suppression that achieves an efficient immune response without damaging the host. Mechanisms of Immune Tolerance ACTIVATION (immunity) SUPPRESSION (tolerance)

More information

Chapter 13: Cytokines

Chapter 13: Cytokines Chapter 13: Cytokines Definition: secreted, low-molecular-weight proteins that regulate the nature, intensity and duration of the immune response by exerting a variety of effects on lymphocytes and/or

More information

Induction of granulysin in CD8 T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1

Induction of granulysin in CD8 T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1 Article Induction of granulysin in T cells by and is suppressed by human immunodeficiency virus-1 A. E. Hogg, G. C. Bowick,, N. K. Herzog, M. W. Cloyd,, and J. J. Endsley,,1 Departments of Microbiology

More information

Challenges in Development and Validation of an Intracellular Cytokine Staining assay

Challenges in Development and Validation of an Intracellular Cytokine Staining assay Challenges in Development and Validation of an Intracellular Cytokine Staining assay Jenny Hendriks, Crucell Hatching @ EBF, Brussels, June 202 www.crucell.com Vaccines vs Protein therapeutics Protein

More information

Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection

Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection Jennifer Martinez 1, Xiaopei Huang 2, Yiping Yang 1,2 * 1 Department of Immunology, Duke University

More information

A VACCINE FOR HIV BIOE 301 LECTURE 10 MITALI BANERJEE HAART

A VACCINE FOR HIV BIOE 301 LECTURE 10 MITALI BANERJEE HAART BIOE 301 LECTURE 10 MITALI BANERJEE A VACCINE FOR HIV HIV HAART Visit wikipedia.org and learn the mechanism of action of the five classes of antiretroviral drugs. (1) Reverse transcriptase inhibitors (RTIs)

More information

Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5α expression in PBMC

Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5α expression in PBMC Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5α expression in PBMC The Harvard community has made this article openly available. Please

More information

The potential role of PD-1/PD-L1 blockade in HIV Remission and Cure Strategies

The potential role of PD-1/PD-L1 blockade in HIV Remission and Cure Strategies The potential role of PD-1/PD-L1 blockade in HIV Remission and Cure Strategies Stephen Mason Director, Discovery Virology Bristol-Myers Squibb Community Cure Workshop 2015 Sunday, Feb 22, 2015 Seattle,

More information

Supporting Information

Supporting Information Supporting Information Idoyaga et al. 10.1073/pnas.0812247106 SSC a) Single cell suspension 99 Aqua b) Live cells 96 -W c) Singlets 92 -A CD19+ER119 d) CD19 ER119 cells 97 CD3 e) CD3 cells 27 f) DX5 cells

More information

La risposta immune all infezione da virus ebola. Chiara Agrati, PhD

La risposta immune all infezione da virus ebola. Chiara Agrati, PhD La risposta immune all infezione da virus ebola Chiara Agrati, PhD Pathogenetic mechanisms This virus infection is able to: - disable the immune system, preventing an effective protective immune response

More information

Pro5 MHC Pentamers. Dr. Jeremy Fry. Copyright ProImmune Limited All Rights Reserved

Pro5 MHC Pentamers. Dr. Jeremy Fry. Copyright ProImmune Limited All Rights Reserved Pro5 MHC Pentamers Dr. Jeremy Fry Pro5 MHC Pentamers The most consistent technology for detecting antigenspecific T cells The most-cited commercially available MHC Multimer Used by most-leading academic

More information

ABSTRACT. HIV-induced immunodeficiency may be mediated by the activation of

ABSTRACT. HIV-induced immunodeficiency may be mediated by the activation of ABSTRACT MEXAS, ANGELA MARIE. CD4 + CD25 + Regulatory T Cells Are Infected and Activated Phenotypically and Functionally During Acute Infection with Feline Immunodeficiency Virus. (Under the direction

More information

BK Virus (BKV) Management Guideline: July 2017

BK Virus (BKV) Management Guideline: July 2017 BK Virus (BKV) Management Guideline: July 2017 BK virus has up to a 60-80% seroprevalence rate in adults due to a primary oral or respiratory exposure in childhood. In the immumocompromised renal transplant

More information

Tumors arise from accumulated genetic mutations. Tumor Immunology (Cancer)

Tumors arise from accumulated genetic mutations. Tumor Immunology (Cancer) Tumor Immunology (Cancer) Tumors arise from accumulated genetic mutations Robert Beatty MCB150 Mutations Usually have >6 mutations in both activation/growth factors and tumor suppressor genes. Types of

More information

Supplementary Figure 1. IL-12 serum levels and frequency of subsets in FL patients. (A) IL-12

Supplementary Figure 1. IL-12 serum levels and frequency of subsets in FL patients. (A) IL-12 1 Supplementary Data Figure legends Supplementary Figure 1. IL-12 serum levels and frequency of subsets in FL patients. (A) IL-12 serum levels measured by multiplex ELISA (Luminex) in FL patients before

More information

Mary ET Boyle, Ph. D. Department of Cognitive Science UCSD

Mary ET Boyle, Ph. D. Department of Cognitive Science UCSD ? Mary ET Boyle, Ph. D. Department of Cognitive Science UCSD Christian S Lobsiger & Don W Cleveland (2007) Nature Neuroscience 10, 1355-1360 Astrocytes: interlinked gatekeepers of glutamate astrocytes

More information

Adaptive Immunity: Specific Defenses of the Host

Adaptive Immunity: Specific Defenses of the Host 17 Adaptive Immunity: Specific Defenses of the Host SLOs Differentiate between innate and adaptive immunity, and humoral and cellular immunity. Define antigen, epitope, and hapten. Explain the function

More information

Establishment and Targeting of the Viral Reservoir in Rhesus Monkeys

Establishment and Targeting of the Viral Reservoir in Rhesus Monkeys Establishment and Targeting of the Viral Reservoir in Rhesus Monkeys Dan H. Barouch, M.D., Ph.D. Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Ragon Institute of MGH, MIT,

More information

Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques

Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques Related article, page 544 Brief report Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques Nichole R. Klatt, 1 Lauren A. Canary, 1 Xiaoyong

More information

Hematology MUHAMMAD M. KHURRAM* SAGHIR A. JAFRI* ABDUL MANNAN** AFTAB NADEEM*** ASIF JAMAL*

Hematology MUHAMMAD M. KHURRAM* SAGHIR A. JAFRI* ABDUL MANNAN** AFTAB NADEEM*** ASIF JAMAL* Hematology FREQUENCY OF ABERRANT EXPRESSION OF CD MARKERS IN CASES OF ACUTE LEUKEMIA MUHAMMAD M. KHURRAM* SAGHIR A. JAFRI* ABDUL MANNAN** AFTAB NADEEM*** ASIF JAMAL* SUMMARY: In the present study 100 patients

More information

John Langowski, Ph.D. Nektar Therapeutics San Francisco, CA USA

John Langowski, Ph.D. Nektar Therapeutics San Francisco, CA USA NKTR-38: a selective, first-in-class IL-2 pathway agonist which increases number and suppressive function of regulatory T cells for the treatment of immune inflammatory disorders John Langowski, Ph.D.

More information

Update: New Treatment Modalities

Update: New Treatment Modalities ASH 2008 Update: New Treatment Modalities ASH 2008: Update on new treatment modalities GA101 Improves tumour growth inhibition in mice and exhibits a promising safety profile in patients with CD20+ malignant

More information

Research Article The Function of CD3 + CD56 + NKT-Like Cells in HIV-Infected Individuals

Research Article The Function of CD3 + CD56 + NKT-Like Cells in HIV-Infected Individuals BioMed Research International, Article ID 863625, 9 pages http://dx.doi.org/1.1155/214/863625 Research Article The Function of CD3 + CD56 + NKT-Like Cells in HIV-Infected Individuals Yongjun Jiang, 1,2

More information

G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics

G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics Journal of Physics: Conference Series PAPER OPEN ACCESS G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics To cite

More information

Elevated Th17 and IL-23 in Hypertensive Patients with Acutly Increased Blood Pressure

Elevated Th17 and IL-23 in Hypertensive Patients with Acutly Increased Blood Pressure American Journal of Immunology 8 (2): 27-32, 2012 ISSN 1553-619X 2012 Science Publications Elevated Th17 and IL-23 in Hypertensive Patients with Acutly Increased Blood Pressure 1 Junxian Wang, 1 Jianying

More information

Immune surveillance hypothesis (Macfarlane Burnet, 1950s)

Immune surveillance hypothesis (Macfarlane Burnet, 1950s) TUMOR-IMMUNITÄT A.K. Abbas, A.H. Lichtman, S. Pillai (6th edition, 2007) Cellular and Molecular Immunology Saunders Elsevier Chapter 17, immunity to tumors Immune surveillance hypothesis (Macfarlane Burnet,

More information

Innate Immunity. Bởi: OpenStaxCollege

Innate Immunity. Bởi: OpenStaxCollege Innate Immunity Bởi: OpenStaxCollege The vertebrate, including human, immune system is a complex multilayered system for defending against external and internal threats to the integrity of the body. The

More information

Secondary Zika virus infection do not support evidences of Antibody-Dependent Enhancement in vivo in dengue pre-exposed rhesus macaques

Secondary Zika virus infection do not support evidences of Antibody-Dependent Enhancement in vivo in dengue pre-exposed rhesus macaques University of Puerto Rico Medical Sciences Campus Caribbean Primate Research Center Secondary Zika virus infection do not support evidences of Antibody-Dependent Enhancement in vivo in dengue pre-exposed

More information

Normally occurring NKG2D + CD4 + T cells are immunosuppressive and inversely correlated with disease activity in juvenileonset

Normally occurring NKG2D + CD4 + T cells are immunosuppressive and inversely correlated with disease activity in juvenileonset ARTICLE Normally occurring NKG2D + CD4 + T cells are immunosuppressive and inversely correlated with disease activity in juvenileonset lupus Zhenpeng Dai, 1 Cameron J. Turtle, 1 Garrett C. Booth, 1 Stanley

More information

Refractory celiac disease (RCD) KASSEM BARADA LEBANESE SOCIETY OF GASTROENTEROLOGY NOVEMBER, 2014

Refractory celiac disease (RCD) KASSEM BARADA LEBANESE SOCIETY OF GASTROENTEROLOGY NOVEMBER, 2014 Refractory celiac disease (RCD) KASSEM BARADA LEBANESE SOCIETY OF GASTROENTEROLOGY NOVEMBER, 2014 Case scenario (1) A 49 year woman presents with intermittent watery diarrhea and bloating of two years

More information

Intestinal Microflora and Immunoregulation

Intestinal Microflora and Immunoregulation Intestinal Microflora and Immunoregulation Monica Boirivant Istituto Superiore di Sanità Roma Microflora-immune cells interactions Ethanol AT 12 T Effect of ir Ethanol 5% administration 115 weight (% of

More information

High Expression of NKG2A/CD94 and Low Expression of Granzyme B Are Associated with Reduced Cord Blood NK Cell Activity

High Expression of NKG2A/CD94 and Low Expression of Granzyme B Are Associated with Reduced Cord Blood NK Cell Activity Cellular & Molecular Immunology 377 Article High Expression of NKG2A/CD94 and Low Expression of Granzyme B Are Associated with Reduced Cord Blood NK Cell Activity Yanyan Wang 1, 2, Han Xu 1, 2, Xiaodong

More information

Characterization of naïve immune cell subsets important in HIV/SIV pathogenesis as a baseline for RNASeq deconvolution

Characterization of naïve immune cell subsets important in HIV/SIV pathogenesis as a baseline for RNASeq deconvolution Boston University OpenBU Theses & Dissertations http://open.bu.edu Boston University Theses & Dissertations 2015 Characterization of naïve immune cell subsets important in HIV/SIV pathogenesis as a baseline

More information

Supplementary Figure 1. Expression of EPO and EPOR during self-limited versus delayed

Supplementary Figure 1. Expression of EPO and EPOR during self-limited versus delayed Supplementary Figure 1. Expression of EPO and EPOR during self-limited versus delayed inflammation resolution. a: Flow cytometry analysis showing the electronic gating strategy used to identify peritoneal

More information

Successful flow cytometric immunophenotyping of body fluid specimens

Successful flow cytometric immunophenotyping of body fluid specimens Successful flow cytometric immunophenotyping of body fluid specimens Fiona E. Craig, MD Division of Hematopathology Mayo Clinic Arizona 2017 MFMER slide-1 Financial disclosure No conflicts 2017 MFMER slide-2

More information

PK/PD: Gut vs Genital Tract

PK/PD: Gut vs Genital Tract PK/PD: Gut vs Genital Tract Mackenzie L ottrell, PharmD, MS, BPS, AAHIVP Research Assistant Professor, N Eshelman School of Pharmacy Assistant Director, linical Pharmacology and Analytical hemistry ore,

More information

Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration

Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration Irini Sereti 1 *, Jacob D. Estes 2, William L. Thompson 1, David R. Morcock 2, Margaret A. Fischl 3, Thérèse

More information

Characterization of T-Cell Responses in Macaques Immunized with a Single Dose of HIV DNA Vaccine

Characterization of T-Cell Responses in Macaques Immunized with a Single Dose of HIV DNA Vaccine JOURNAL OF VIROLOGY, Feb. 2010, p. 1243 1253 Vol. 84, No. 3 0022-538X/10/$12.00 doi:10.1128/jvi.01846-09 Copyright 2010, American Society for Microbiology. All Rights Reserved. Characterization of T-Cell

More information

Supplemental Information. CD4 + CD25 + Foxp3 + Regulatory T Cells Promote. Th17 Cells In Vitro and Enhance Host Resistance

Supplemental Information. CD4 + CD25 + Foxp3 + Regulatory T Cells Promote. Th17 Cells In Vitro and Enhance Host Resistance Immunity, Volume 34 Supplemental Information D4 + D25 + + Regulatory T ells Promote Th17 ells In Vitro and Enhance Host Resistance in Mouse andida albicans Th17 ell Infection Model Pushpa Pandiyan, Heather

More information

A. SPECIFIC AIMS test the hypothesis that these alleles restrict SIV-specific CD8+ T cell specificities that reduce in vitro SIV replication

A. SPECIFIC AIMS test the hypothesis that these alleles restrict SIV-specific CD8+ T cell specificities that reduce in vitro SIV replication A. SPECIFIC AIMS A.R21: Correlates of protective cellular immunity in MHC-identical, SIV+ Mauritian macaques After more than a quarter century of study, we do not have an effective human immunodeficiency

More information

HVTN Laboratory Program: Immunogenicity and Research Assays

HVTN Laboratory Program: Immunogenicity and Research Assays HVTN Laboratory Program: Immunogenicity and Research Assays Erica Andersen-Nissen, PhD Director, Cape Town HVTN Immunology Laboratory Considerations for a Pan-African HIV Vaccine Development Agenda Kigali,

More information

Co-evolution of host and pathogen: HIV as a model. Can Keşmir Theoretical Biology/Bioinformatics Utrecht University, NL

Co-evolution of host and pathogen: HIV as a model. Can Keşmir Theoretical Biology/Bioinformatics Utrecht University, NL Co-evolution of host and pathogen: HIV as a model Can Keşmir Theoretical Biology/Bioinformatics Utrecht University, NL c.kesmir@bio.uu.nl Outline Does HIV adapt to monomorphic human molecules? Polymorphic

More information

Overview of Transplantation Immunology Research at the Starzl Transplantation Institute for Incoming Students

Overview of Transplantation Immunology Research at the Starzl Transplantation Institute for Incoming Students Overview of Transplantation Immunology Research at the Starzl Transplantation Institute for Incoming Students Starzl Transplantation Institute & Departments of Surgery and Immunology, University of Pittsburgh

More information

Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections

Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections Jacob D. Estes 1 *, Levelle D. Harris 2, Nichole R. Klatt 2, Brian Tabb

More information

Follicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development.

Follicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development. Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Follicular Lymphoma 1. Characterized by t(14:18) translocation 2. Ig heavy

More information