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)-β 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-β and a main early producer of IL-10 in response to viral infection. Here, we evaluated the percentages of IL-10(+) and TGF-β(+) NK cells in HIV-infected patients relative to healthy controls (HCs). METHODS: Study participants (n = 63) included 31 antiretroviral treatment (ART)-naïve HIV-infected patients, 17 ART-treated HIV-infected patients, and 15 HIV-negative HCs. Expression of IL-10 or TGF-β in NK cells was examined by flow cytometry, and the influences of recombinant IL-10 (rIL-10) or recombinant TGF-β (rTGF-β) on NK cell function were investigated in vitro. RESULTS: Compared with HCs, ART-naïve HIV-infected patients had increased percentages of IL-10(+) (2.0% vs. 0.4%, p = 0.015) and TGF-β(+) (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-β(+) NK cells were positively correlated (r = 0.388; p = 0.010). The results of in vitro experiments demonstrated that rIL-10 and rTGF-β inhibited NK cell CD107a expression (p = 0.037 and p = 0.024, respectively), IFN-γ 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-β(+) NK cells are increased in HIV-infected patients, and that rIL-10 and/or rTGF-β can inhibit NK cell functions in vitro, providing a potential therapeutic target for strategies aimed at combating HIV infection.