IL-10+ NK and TGF-β+ NK cells play negative regulatory roles in HIV infection
Autor: | Jing Liu, Shi Qian, Yajing Fu, Zining Zhang, Hong Shang, Junjie Xu, Xiaowan Yin, Xi Chen, Meichen Ma, Yongjun Jiang, Xiaojuan Sun, Xiaoxu Han, Mei Yang |
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Rok vydání: | 2018 |
Předmět: |
CD4-Positive T-Lymphocytes
Male 0301 basic medicine Chemokine HIV Infections Granzymes 0302 clinical medicine Transforming Growth Factor beta Cytotoxic T cell Medicine Interferon gamma IFN-γ Cells Cultured biology Interleukin Recombinant Proteins Interleukin-10 Killer Cells Natural Interleukin 10 Infectious Diseases Anti-Retroviral Agents IL-10 RNA Viral Research Article medicine.drug Adult TGF-β Immune regulation NK lcsh:Infectious and parasitic diseases Interferon-gamma Young Adult 03 medical and health sciences Lysosomal-Associated Membrane Protein 1 Humans lcsh:RC109-216 Perforin business.industry HIV CD4 Lymphocyte Count Granzyme B Antiretroviral treatment 030104 developmental biology Granzyme Case-Control Studies Immunology Leukocytes Mononuclear biology.protein business 030215 immunology |
Zdroj: | BMC Infectious Diseases, Vol 18, Iss 1, Pp 1-10 (2018) BMC Infectious Diseases |
ISSN: | 1471-2334 |
Popis: | 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. |
Databáze: | OpenAIRE |
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