Sunday, January 16, 2011

Antiretroviral therapy induced functional recovery of HIV specific CD4 cells

Tsalimalma K, Kordossis T, Choremi-Papadopoulou E.:
Immunology Department, General Hospital Athens, Greece

Abstract
Prolonged antiretroviral treatment (ART) significantly changes the cytokine secretion capacities of HIV-1 specific T cells. However it is unclear whether these changes result from decreased viremia or they correspond to true functional recovery of viral specific immune response. To study this issue, we analyzed the quantitative and qualitative differences of HIV-1 specific and polyclonal CD4+ and CD8+ T cells between 26 naive and 52 treated individuals.

HIV-1 Gag and SEB reactive T cells were determined by flowcytometric intracellular secretion of IFN-γ or/and ΙL-2. ART resulted in increase of single IL-2 and decrease of single IFN-γ secreting HIV-1 CD4+ T cells, while both cytokines secreting HIV-1 CD4+ T cells were presented in comparable frequencies in both groups. Viral loads correlated negatively with single IL-2 and positively with single IFN-γ secreting HIV-1 CD4+ cells. Single IL-2 HIV-1 CD4+ T cells correlated positively with both cytokines secreting polyclonal CD8+ T cells. By qualitative analysis a dominant IL-2 HIV-1 CD4+ T cell response (>70% single IL-2), was identified only in ART suppressed patients, who also generated increased dual specific polyclonal CD8+ T cells. Polyfunctional HIV-1 CD4+ T cell responses were detected even in naive individuals with high viremia.

In conclusion, the presence of dominant IL-2 HIV-1 CD4+ T cell response, associated with increased CD8+ T cells capable to produce IL-2 indicates that the recovery of HIV-1 specific CD4+ T cell functionality under ART is a feasible goal. Further, polyfunctional HIV-1 CD4+ T cell responses seem not to be directly involved in viral replication control.

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