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
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
Externí odkaz: