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Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8⁺ T Cells.

ABSTRACT: 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.

SUBMITTER: Kwaa AKR

PROVIDER: S-EPMC6340025 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8<sup>+</sup> T Cells.

Kwaa Abena K R AKR Talana Chloe A G CAG Blankson Joel N JN

Journal of virology 20190117 3

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<sup>+</sup> T cell and ...[more]

PMID: 30404799

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Project description:Increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans, and as such, novel approaches harnessing the anti-HIV-1 function of both T cells and NK cells represent attractive options to improve future HIV-1 immunotherapies. Chronic progressive HIV-1 infection has been associated with a loss of CD4(+) T helper cell function and with the accumulation of anergic NK cells. As several studies have suggested that cytokines produced by CD4(+) T cells are required to enhance NK cell function in various infection models, we hypothesized that reconstitution of HIV-1-specific CD4(+) T-cell responses by therapeutic immunization would restore NK cell activity in infected individuals. Using flow cytometry, we examined the function of CD4(+) T cells and NK cells in response to HIV-1 in subjects with treated chronic HIV-1 infection before and after immunization with an adjuvanted HIV-1 Gp120/NefTat subunit protein vaccine candidate provided by GlaxoSmithKline. Vaccination induced an increased expression of interleukin-2 (IL-2) by Gp120-specific CD4(+) T cells in response to HIV-1 peptides ex vivo, which was associated with enhanced production of gamma interferon (IFN-?) by NK cells. Our data show that reconstitution of HIV-1-specific CD4(+) T-cell function by therapeutic immunization can enhance NK cell activity in HIV-1-infected individuals.NK cells are effector cells of the innate immune system and are important in the control of viral infection. Recent studies have demonstrated the crucial role played by NK cells in controlling and/or limiting acquisition of HIV-1 infection. However, NK cell function is impaired during progressive HIV-1 infection. We recently showed that therapeutic immunization of treated HIV-1-infected individuals reconstituted strong T-cell responses, measured notably by their production of IL-2, a cytokine that can activate NK cells. The current study suggests that reconstitution of T-cell function by therapeutic vaccination can enhance NK cell activity in individuals with chronic HIV-1 infection. Our findings provide new insights into the interplay between adaptive and innate immune mechanisms involved in HIV-1 immunity and unveil opportunities to harness NK cell function in future therapeutic vaccine strategies to target HIV-1.

Dataset Information

Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8⁺ T Cells.

Publications

Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8<sup>+</sup> T Cells.

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Dataset Information

Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8+ T Cells.

Publications

Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8<sup>+</sup> T Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Interferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8⁺ T Cells.