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Human CD8+CD28- T suppressor cells expanded by common gamma chain (?c) cytokines retain steady allospecific suppressive capacity in vivo.

ABSTRACT: BACKGROUND:CD8+CD28- T suppressor (Ts) cells play critical role in transplant tolerance. Our previous study has generated CD8+CD28- Ts cells in vitro which exert robust allospecific suppressive capacity in vitro. RESULTS:CD8+CD28- Ts cells were expanded by stimulating human CD8+ T cells with allogeneic antigen presenting cells in the presence of the common gamma chain cytokines IL-2, IL-7 and IL-15 in vitro, and were further verified in vitro through day 7 to 11 for their persistency of the allospecific suppressive capacity. When CD8+CD28- Ts cells were adoptively transferred into NOG mice, their capacity to inhibit CD4+ T cell proliferation in allospecific manner remained potent on 11?days after their injection. The mechanisms for expansion of CD8+CD28- Ts cells by the common gamma chain cytokines were investigated. These included promoting CD8+CD28- T cells proliferation, converting CD8+CD28+ T cells to CD8+CD28- T cells and decreasing CD8+CD28- T cell death. Furthermore, the expanded CD8+CD28- Ts cells showed upregulation of the co-inhibitory molecule Tim-3 and down-regulation of the cytotoxic molecule granzyme B. CONCLUSIONS:In summary, these results demonstrated that the in vitro-expanded human CD8+CD28- T cells retained potent allospecific suppressive capacity in vivo and depicted multiple mechanisms for the expansion of Ts cells, which might promote further bench to clinic research.

SUBMITTER: Liu G

PROVIDER: S-EPMC7189520 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Human CD8<sup>+</sup>CD28<sup>-</sup> T suppressor cells expanded by common gamma chain (γc) cytokines retain steady allospecific suppressive capacity in vivo.

Liu Guihuan G Yu Yuming Y Feng Fu F Zhu Ping P Zhang Hua H Zhang Danni D Feng Xiaoqiang X Zhang Zedan Z Liu Yanjun Y

BMC immunology 20200429 1

<h4>Background</h4>CD8<sup>+</sup>CD28<sup>-</sup> T suppressor (Ts) cells play critical role in transplant tolerance. Our previous study has generated CD8<sup>+</sup>CD28<sup>-</sup> Ts cells in vitro which exert robust allospecific suppressive capacity in vitro.<h4>Results</h4>CD8<sup>+</sup>CD28<sup>-</sup> Ts cells were expanded by stimulating human CD8<sup>+</sup> T cells with allogeneic antigen presenting cells in the presence of the common gamma chain cytokines IL-2, IL-7 and IL-15 in vit ...[more]

PMID: 32349664

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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

Human CD8+CD28- T suppressor cells expanded by common gamma chain (?c) cytokines retain steady allospecific suppressive capacity in vivo.

Publications

Human CD8<sup>+</sup>CD28<sup>-</sup> T suppressor cells expanded by common gamma chain (γc) cytokines retain steady allospecific suppressive capacity in vivo.

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