AUTHOR=Xie Zhe , Zheng Jiajia , Wang Yuya , Li Dan , Maermaer Tuohutaerbieke , Li Yuantao , Tu Jing , Xu Qiang , Liang Hua , Cai Weiping , Shen Tao 

TITLE=Deficient IL-2 Produced by Activated CD56+ T Cells Contributes to Impaired NK Cell-Mediated ADCC Function in Chronic HIV-1 Infection

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01647

DOI=10.3389/fimmu.2019.01647

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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<sup>+</sup> T cells on NK-ADCC response.</p><p><bold>Results:</bold> 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<sup>+</sup> T cells activated through antibody-dependent manner. The capability of NK-ADCC could be weakened by blocking IL-2 secretion from activated CD56<sup>+</sup> T cells. Although no difference of frequencies of CD56<sup>+</sup> T cells was found between HIV-1-infected patients and healthy controls, deficient IL-2 secretion from activated CD56<sup>+</sup> T were found in chronic HIV-1 infection.</p><p><bold>Conclusions:</bold> The impaired ability of activated CD56<sup>+</sup> T cells to secreting IL-2 might contribute to the attenuated NK cell-mediated ADCC function in HIV-1 infection.</p>