Deficient IL-2 produced by activated CD56+ T cells contributes to impaired NK cell-mediated ADCC function in chronic HIV-1 infection

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Abstract

Background: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in human immunodeficiency virus type-1 (HIV-1) disease progression. However, the potential mechanisms that affecting NK-mediated ADCC response are still not well-elucidated. Methods: Antigen-antibody complex model of Ab-opsonized P815 cells was adopted to induce a typical non-specific ADCC response. The capacities of HIV-1 specific NK-ADCC were measured by using the combination model of gp120 protein and plasma of HIV-1 elite controllers. The levels of plasma cytokine were measured by ELISA. Anti-IL-2 blocking antibody was used to analyze the impact of activated CD56+ T cells on NK-ADCC response. Results: IL-2, IL-15, IFN-α, and IFN-β could effectively enhance the non-specific and HIV-1-specific NK-ADCC responses. Compared with healthy controls, HIV-1-infected patients showed decreased plasma IL-2 levels, while no differences of plasma IFN-α, IL-15, and IFN-β were presented. IL-2 production was detected from CD56+ T cells activated through antibody-dependent manner. The capability of NK-ADCC could be weakened by blocking IL-2 secretion from activated CD56+ T cells. Although no difference of frequencies of CD56+ T cells was found between HIV-1-infected patients and healthy controls, deficient IL-2 secretion from activated CD56+ T were found in chronic HIV-1 infection. Conclusions: The impaired ability of activated CD56+ T cells to secreting IL-2 might contribute to the attenuated NK cell-mediated ADCC function in HIV-1 infection.

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Xie, Z., Zheng, J., Wang, Y., Li, D., Maermaer, T., Li, Y., … Shen, T. (2019). Deficient IL-2 produced by activated CD56+ T cells contributes to impaired NK cell-mediated ADCC function in chronic HIV-1 infection. Frontiers in Immunology, 10(JULY). https://doi.org/10.3389/fimmu.2019.01647

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