30 1, 1, 2, 3 1. ( ), 201508; 2., 200040; 3., 200032 : ( AIDS) ( HIV) 20 90,,,,,, AIDS, CD4 + T ( CTL), HIV, : ; ; Therapeutic strategies for immune reconstitution in acquired immunodeficiency syndrome SUN Fu-Yan 1, LU Hong-Zhou 1, 2, 3 1. Department of Infectious Disease, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai 201508, China; 2. Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai 200040, China; 3. Department of Medical Science, Shanghai Medical College, Fudan University, Shanghai 200032, China Abstract: Acquired immunodeficiency syndrome ( AIDS) is caused by the human immunodeficiency virus ( HIV), an infection that destroys the body s immune system. It was thought that the immunodeficiency observed in this disease was irreversible, despite antiretroviral therapy. Since the 1990s, however, highly active antiretroviral therapy ( HAART) has been used for clinical treatment. It has since been realized that HAART not only suppresses HIV replication but also reconstitutes the immune function in AIDS patients. Recent research has asked how to effectively reconstitute the immune function in AIDS patients, which involves facilitating the ability of the immune system to normal or near normal levels through anti-viral strategies and adoptive immunotherapy among other approaches. The goal of immune reconstitution is dissipation of the clinical symptoms of AIDS, as evidenced by a decrease in the incidence of AIDS-related opportunistic infections and tumors and a decline in rates of mortality. Through technological developments and better understanding of the immunopathogenesis and mechanisms of immune reconstitution, it is possible to improve the level and function of CD4 + T cells and to enhance HIV-specific cytotoxic T lymphocyte( CTL) immune responses. At present, a number of new therapies and strategies are entering clinical studies, including the use of various cytokines and therapeutic HIV vaccines. Key words: Acquired immunodeficiency syndrome; Therapeutic vaccine; Immune reconstitution ( acquired immunodeficiency syndrome, AIDS), ( human immunodeficiency virus, HIV) : ( 2008ZX10001-008) :, E-mail: luhongzhou@ fudan. edu. cn Corresponding author: LU Hong-Zhou, E-mail: luhongzhou@ fudan. edu. cn AIDS, HIV RNA, CD4 + ( CD4 + T ), ( ),, 20 90, ( highly active antiretroviral therapy, HAART),
2009 3 4 1 Journal of Microbes and Infection, March 2009, Vol. 4, No. 1 31 HAART HIV, AIDS, AIDS,, AIDS 1 AIDS 20 90 HAART, AIDS, AIDS AIDS, HIV, : CD4 + T ; CD4 + T ;,, AIDS 2 2. 1 HAART AIDS T HAART, CD4 + T HAART, 2 ( nucleoside reverse transcriptase inhibitor, NRTI) 1 ( non-nrti, NNRTI), 2 NRTI 1 ( protease inhibitor, PI) HAART T 3 [ 1] : T,,,, ; T CD4 + T ; CD4 + T CD8 + T,, T, CD4 + T T, T T, T HAART, T,, T ; 2 ( interleukin-2, IL-2) [ 2] HAART HIV,, AIDS, T [ 3] HAART HIV / AIDS : HAART,, HIV, T [ 2],, CD4 + HIV [ 4 ], HIV, CD8 + T HIV [ 4] HAART 2. 2 T 2. 2. 1 IL-2 IL-7 IL-15 IL-12, IL-2 IL-2 T, T, HIV IL-2, HAART IL-2 CD4 + T T, HAART IL-2 CD4 +,, : T T ; T, T T ;,
32 T IL-7 / CD127 ( IL-7R) IL-2 1, CD4 + T, IL-2 CD38 CD8 + T, HIV [ 5 ] IL-7 IL-15 T, HIV IL-7 T, T [ 6] HIV T CD127, CD8 + T, CD127 IL-7 T [ 7 ], HIV CD8 + T CD127, CD8 + T, CD4 + T T, CD127 - T CD38, CD127 T HAART CD127 CD4 + T ( T ), CD8 + T ; CD38 CD4 + T CD8 + T, CD127, CD4 + T CD127 IL-7, HAART CD4 + T, IL-7 /CD127 [ 8 ], CD25( IL- 2R) CD127( IL-7R) CD4 + T 3 : CD127 + CD25 low / - CD127 - CD25 - CD127 low CD25 high, HIV CD4 + CD127 - CD25 - T CD127 + T, CD127 -, CD127 - T T IL-7, IL-7 / CD127 [ 9 ] IL-15 ( antigen presenting cell, APC), CD8 + T [ 10] T ( CD38 CTLA-4 ), 2. 2. 2 HIV HIV AIDS, AIDS,, HIV HIV, CD8 + T HIV ; B, HIV, HIV HIV AIDS DNA,, DNA, Megati, RNA HIV-1 env gp160 DNA env, env env HIV [ 11] IL-7 IL-15 HIV-1 DermaVir Gag T, IL-15, DermaVir Gag CD8 + T, [ 12 ] Merck s 2. 2. 3,,, CD4 + T ( structured treatment interruption, STI),,,, Dianzani ( interferon, IFN), IFN, 4, IFN 3 /4 2 [ 1 3] IL-2,,, STI
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