Impact of γ-chain cytokines on T cell homeostasis in HIV-1 infection: Therapeutic implications: Symposium

Abstract

Gougeon M-L, Chiodi F (Institut Pasteur, Paris, France, and Karolinska Institutet, Stockholm, Sweden) Impact of γ-chain cytokines on T cell homeostasis in HIV-1 infection: therapeutic implications (Symposium). J Intern Med 2010; 267: 502-514. 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 γ-chain cytokines has been used in HIV-1-infected patients during concomitant HAART. In this review, we summarize the role of γ-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 γ-chain cytokines. © 2010 Blackwell Publishing Ltd.