Increased NKG2A found in cytotoxic natural killer subset in HIV-1 patients with advanced clinical status.
OBJECTIVE
To investigate the expression of NKG2A on cytotoxic natural killer (NK) cells in HIV-1-infected patients.


METHODS
A cross-sectional study was conducted to investigate the NKG2A expression on NK cell subsets among HIV-infected individuals at different clinical stages and HIV negative controls.


METHODS
113 HIV-1 infected and 43 uninfected individuals were enrolled in this study. The HIV-1 infected patients were further categorized into three groups, CD4 cell count > 500 cells/microl (n = 44), CD4 cell count of 200-500 cells/microl (n = 49) and CD4 cell count < 200 cells/microl (n = 20). Flow cytometry was used to determine the expression of NKG2A on NK cell subsets. A flow-based assay was employed to quantify the NK cytotoxicity.


RESULTS
Fewer cytotoxic NK cells and more dysfunctional NK cells were observed in patients with advanced clinical conditions. Higher NKG2A expression level in cytotoxic NK subset were found in later stages HIV infection, 25.6% in groups with CD4 cell count > 500 cells/microl, 40.9% in groups with CD4 cell count 200-500 cells/microl and 48.3% in groups with CD4 cell count < 200 cells/microl. Lower NK mediated cytotoxicity, which was associated with the decrease in cytotoxic NK cell number and higher NKG2A expression on cytotoxic NK subsets, was found in AIDS patients compared with patients at early stage of infection. A reverse association between the percentage of NKG2A positive cells in cytotoxic NK subset and CD4 cell count was observed in all HIV-1 infected groups.


CONCLUSIONS
Fewer cytotoxic NK cells and higher NKG2A expression in cytotoxic NK subset was found in patients in late stage HIV infection. Such a phenomenon may relate to the escape of HIV-1-infected CD4+ T cells from being attacked by NK cells.
Zhang
Ruijun
R
State Key Laboratory for Infectious Diseases Prevention and Control, National Center for AIDS/STD Control and Prevention, China CDC, Beijing, China.
Xu
Jianqing
J
Hong
Kunxue
K
Yuan
Lin
L
Peng
Hong
H
Tang
Haili
H
Ma
Pengfei
P
Zhang
Yuanzhi
Y
Xing
Hui
H
Ruan
Yuhua
Y
Shao
Yiming
Y
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000328:Adult; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D003602:Cytotoxicity, Immunologic; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology; D008297:Male; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic / Q000097:blood*; D055607:Receptors, Natural Killer Cell; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000276:immunology
C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell