Impact of gamma-chain cytokines on T cell homeostasis in HIV-1 infection: therapeutic implications.
CD4(+) T cell lymphocytes are a major target for human immunodeficiency virus type-1 (HIV-1) infection. During this chronic infection, CD4(+) T cell loss (induced through direct viral replication), generalized immune activation and increased susceptibility to apoptosis result in impaired T cell homeostasis with subsequent development of opportunistic infections and cancers. Highly active antiretroviral therapy (HAART) has a well-defined, beneficial effect on HIV-1-related clinical outcome; however, it does not lead to normalization of immune dysregulation. In order to boost both CD4(+) T cell restoration and HIV-1 specific immunity, immunotherapy with gamma-chain cytokines has been used in HIV-1-infected patients during concomitant HAART. In this review, we summarize the role of gamma-chain cytokines, especially interleukin (IL)-2 and IL-7, in influencing T cell homeostasis and proliferation, and discuss how immunotherapy with these cytokines may be beneficial to reconstitute the T cell compartment in the context of HIV-1 infection. The intriguing results of two large trials evaluating the efficacy of IL-2 in restoring immune function during HIV-1 infection are also discussed. In addition, we consider the promises and caveats of the first phase I/II clinical trials with IL-7 in HIV-1-infected patients and the knowledge that is still lacking in the field of T cell reconstitution through gamma-chain cytokines.
Gougeon
M-L
ML
Institut Pasteur, Paris, France. mlgougeo@pasteur.fr
Chiodi
F
F
D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D018121:Receptors, Cytokine / Q000378:metabolism
D044966:Anti-Retroviral Agents; D007376:Interleukin-2; D015851:Interleukin-7; D018121:Receptors, Cytokine