Comparison of the frequency of interleukin (IL)-2-, interferon-gamma-, and IL-4-producing T cells in 2 diseases, human immunodeficiency virus types 1 and 2, with distinct clinical outcomes.
ABSTRACT Human immunodeficiency virus (HIV) type 2 infection is associated with a better clinical outcome, slower rates of CD4 T cell decline, and lower viremia than is HIV-1. This study compares HIV-1 and HIV-2 in regard to the percentages of interleukin (IL)-2-, interferon (IFN)-gamma-, and IL-4-producing cells at the single-cell level, as determined by flow cytometry. At a given degree of CD4 T cell depletion, the frequency of T cells able to produce IL-2 is better preserved in HIV-2 than in HIV-1 infection, particularly within the CD4 T cell subset. As described for HIV-1 immunodeficiency, HIV-2-positive patients exhibit a marked expansion of terminally differentiated effector CD8 T cells (CD28(-)CD27(-)IFN-gamma(+)). However, the proportion of CD8 T cells able to simultaneously produce IL-2 and IFN-gamma is higher in HIV-2 disease. Considering the central role of IL-2 as a lymphocyte proliferative and survival factor, these findings provide a possible immunologic basis for the distinct course of HIV-2 immunodeficiency.
- SourceAvailable from: Francesca Chiodi[Show abstract] [Hide abstract]
ABSTRACT: 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.Journal of Internal Medicine 05/2010; 267(5):502-14. · 6.46 Impact Factor