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CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity during acute and early infection.

ABSTRACT: The strong CD8+ T-cell-mediated HIV-1-suppressive capacity found in a minority of HIV-infected patients in chronic infection is associated with spontaneous control of viremia. However, it is still unclear whether such capacities were also present earlier in the CD8+ T cells from non controller patients and then lost as a consequence of uncontrolled viral replication. We studied 50 patients with primary HIV-1-infection to determine whether strong CD8+ T-cell-mediated HIV suppression is more often observed at that time. Despite high frequencies of polyfunctional HIV-specific CD8+ T-cells and a strong CD4+ T-helper response, CD8+ T-cells from 48 patients lacked strong HIV-suppressive capacities ex vivo. This indicates that the superior HIV-suppressive capacity of CD8+ T-cells from HIV controllers is not a general characteristic of the HIV-specific CD8+ T cell response in primary HIV infection.

SUBMITTER: Lecuroux C

PROVIDER: S-EPMC3612088 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity during acute and early infection.

Lécuroux Camille C Girault Isabelle I Chéret Antoine A Versmisse Pierre P Nembot Georges G Meyer Laurence L Rouzioux Christine C Pancino Gianfranco G Venet Alain A Sáez-Cirión Asier A

PloS one 20130329 3

The strong CD8+ T-cell-mediated HIV-1-suppressive capacity found in a minority of HIV-infected patients in chronic infection is associated with spontaneous control of viremia. However, it is still unclear whether such capacities were also present earlier in the CD8+ T cells from non controller patients and then lost as a consequence of uncontrolled viral replication. We studied 50 patients with primary HIV-1-infection to determine whether strong CD8+ T-cell-mediated HIV suppression is more often ...[more]

PMID: 23555774

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Project description:Current shock-and-kill strategies for the eradication of the HIV-1 reservoir have resulted in blips of viremia but not in a decrease in the size of the latent reservoir in patients on suppressive antiretroviral therapy (ART). This discrepancy could potentially be explained by an inability of the immune system to kill HIV-1-infected cells following the reversal of latency. Furthermore, some studies have suggested that certain latency-reversing agents (LRAs) may inhibit CD8+ T cell and natural killer (NK) cell responses. In this study, we tested the hypothesis that alpha interferon (IFN-?) could improve the function of NK cells from chronic progressors (CP) on ART. We show here that IFN-? treatment enhanced cytokine secretion, polyfunctionality, degranulation, and the cytotoxic potential of NK cells from healthy donors (HD) and CP. We also show that this cytokine enhanced the viral suppressive capacity of NK cells from HD and elite controllers or suppressors. Furthermore, IFN-? enhanced global CP CD8+ T cell cytokine responses and the suppressive capacity of ES CD8+ T cells. Our data suggest that IFN-? treatment may potentially be used as an immunomodulatory agent in HIV-1 cure strategies.IMPORTANCE Data suggest that HIV+ individuals unable to control infection fail to do so due to impaired cytokine production and/cytotoxic effector cell function. Consequently, the success of cure agendas such as the shock-and-kill strategy will probably depend on enhancing patient effector cell function. In this regard, NK cells are of particular interest since they complement the function of CD8+ T cells. Here, we demonstrate the ability of short-course alpha interferon (IFN-?) treatments to effectively enhance such effector functions in chronic progressor NK cells without inhibiting their general CD8+ T cell function. These results point to the possibility of exploring such short-course IFN-? treatments for the enhancement of effector cell function in HIV+ patients in future cure strategies.

Dataset Information

CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity during acute and early infection.

Publications

CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity during acute and early infection.

Similar Datasets

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