IL-10+ NK and TGF-[beta]+ NK cells play negative regulatory roles in HIV infection

• Published in: BMC Infectious Diseases 2018, Vol.18 (1)
• Main Authors: Jiang, Yongjun, Yang, Mei, Sun, Xiaojuan, Chen, Xi, Ma, Meichen, Yin, Xiaowan, Qian, Shi, Zhang, Zining, Fu, Yajing, Liu, Jing, Han, Xiaoxu, Xu, Junjie, Shang, Hong
• Format: Report
• Language: English
• Subjects: Care and treatment; Chemokines; Health aspects; HIV; Infection; Killer cells; Transforming growth factors
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-018-2991-2

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.sup.+ and TGF-[beta].sup.+ NK cells in HIV-infected patients relative to healthy controls (HCs). 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-[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. Compared with HCs, ART-naïve HIV-infected patients had increased percentages of IL-10.sup.+ (2.0% vs. 0.4%, p = 0.015) and TGF-[beta].sup.+ (4.5% vs. 2.1%, p = 0.022) NK cells, and ART-treated patients also had a higher percentage of IL-10.sup.+ NK cells (2.5% vs. 0.4%, p = 0.002). The percentages of IL-10.sup.+ and TGF-[beta].sup.+ 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). Our data suggest that the percentages of IL-10.sup.+ or TGF-[beta].sup.+ 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.