IL-10+ NK and TGF-β+ NK cells play negative regulatory roles in HIV infection

Background: Natural killer (NK) cells play cytotoxic roles by targeting tumor cells or virus infected cells, they also play regulatory roles by secreting cytokines and chemokines. Transforming growth factor (TGF)-beta and interleukin (IL)-10 are important immunosuppressive cytokines potentially related to the immune dysregulation that occurs in the infection of human immunodeficiency virus (HIV). NK cells are an important source of TGF-beta and a main early producer of IL-10 in response to viral infection. Here, we evaluated the percentages of IL-10(+) and TGF-beta(+) NK cells in HIV-infected patients relative to healthy controls (HCs). Methods: Study participants (n = 63) included 31 antiretroviral treatment (ART)-naive HIV-infected patients, 17 ART-treated HIV-infected patients, and 15 HIV-negative HCs. Expression of IL-10 or TGF-beta in NK cells was examined by flow cytometry, and the influences of recombinant IL-10 (rIL-10) or recombinant TGF-beta (rTGF-beta) on NK cell function were investigated in vitro. Results: Compared with HCs, ART-naive HIV-infected patients had increased percentages of IL-10(+) (2.0% vs. 0.4%, p = 0. 015) and TGF-beta(+) (4.5% vs. 2.1%, p = 0.022) NK cells, and ART-treated patients also had a higher percentage of IL-10(+) NK cells (2.5% vs. 0.4%, p = 0.002). The percentages of IL-10(+) and TGF-beta(+) NK cells were positively correlated (r = 0.388; p = 0. 010). The results of in vitro experiments demonstrated that rIL-10 and rTGF-beta inhibited NK cell CD107a expression (p = 0.037 and p = 0.024, respectively), IFN-gamma secretion (p = 0.006, p = 0.016, respectively), and granzyme B release after stimulation (p = 0.014, p = 0.040, respectively). Conclusions: Our data suggest that the percentages of IL-10(+) or TGF-beta(+) NK cells are increased in HIV-infected patients, and that rIL-10 and/or rTGF-beta can inhibit NK cell functions in vitro, providing a potential therapeutic target for strategies aimed at combating HIV infection.