[Upregulated PD-1 on CD8+T cells is positively correlated with activation of T cells during HIV-1 infection].
Objective To investigate the expressions of programmed death-1 (PD-1), CD38, human leukocyte antigen DR (HLA-DR) and anligen KI-67(ki67) on CD8+T cells, and the correlation between PD-1/PD-L1 pathway and activation, immunodepletion during HIV-1 infection. Methods Peripheral blood mononuclear cells were isolated by density gradient centrifugation from 87 HIV-1 patients and 22 healthy controls. The expression levels of PD-1, CD38, HLA-DR and ki67 on CD8+T cells were detected by flow cytometry. Furthermore, we evaluated the production of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) in CD8+T cells by blocking PD-1/PD-L1 pathway in the presence of PD-L1 mAb. Results Compared with healthy controls, HIV-1 infection resulted in a significant increase in PD-1 expression on CD8+T cells. Correlation analysis showed that PD-1 expression on CD8+T cell was positively associated with HIV-1 viral loading (VL) and negatively associated with the number of CD4+T cells. Furthermore, PD-1 expression was positively correlated with CD38 and HLA-DR expressions on CD8+T cells in HIV-1 infected patients. There was no association between PD-1 and ki67 expression on CD8+T cells in HIV-1 infected patients. Blockage of the PD-1/PD-L1 pathway increased TNF-α and IFN-γ production in CD8+T cells. Conclusion PD-1 expression on CD8+T cells is significantly upregulated during HIV-1 infection. PD-1 expression is correlated with CD8+T cell inhibition, immunodepletion and disease progression. Moreover, the blockage of PD-1/PD-L1 pathway can restore the function of CD8+T cells in HIV-1 patients.
Guangxi Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models, Nanning 530001; Shanghai Center for Disease Control and Prevention, Shanghai 200336, China.
Jian
J
Xiao
Guangxi Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models, Nanning 530001, China.
Xian
X
Liu
Shanghai Center for Disease Control and Prevention, Shanghai 200336, China.
Xiaolei
X
Yu
Shanghai Center for Disease Control and Prevention, Shanghai 200336, China.
Yuan
Y
Dong
Shanghai Center for Disease Control and Prevention, Shanghai 200336, China.
Xuqin
X
Wang
Guangxi Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models, Nanning 530001, China. *Corresponding authors, E-mail: lj986771558@163.com.
Jing
J
Leng
Wuhan Institute of Virology, Chinese Academy of Science, Wuhan 430071, China. *Corresponding authors, E-mail: ryang@wh.iov.cn.
Rongge
R
Yang
Shanghai Center for Disease Control and Prevention, Shanghai 200336, China. *Corresponding authors, E-mail: wangying2000@163.com.
Ying
Y
Wang
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation; D055815:Young Adult
D006684:HLA-DR Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma