NKG2C Research Articles

Natural killer cell receptors and human cytomegalovirus infection

Human cytomegalovirus(HCMV)infection is quite prevalent in population.HCMV triggers important disorders in pregnant women, immune-compromised individuals and organ-transplant patients.For decades, more and more scholars believe that NK cells are important immune cells against HCMV.The activity of NK cells largely depends on the balance between the signals transducted by inhibitory receptors and activatory receptors, therefore the study of NK receptors is of great importance.It may be helpful to the basic research and clinical treatment of HCMV infection.Here, this paper reviews the changes and the molecular mechanism of NK receptors in the control of HCMV infection. Key words: Human cytomegalovirus; Natural killer cell; Receptors; NKG2A; NKG2C; NKG2D

Analysis of the phenotypes and the function of CD56+ T cells during primary HIV-1 infection

Objective To investigate the changes of phenotypes and function of CD56+ T cells during primary HIV-1 infection and their relationship with disease progression. Methods Peripheral blood mononuclear cells (PBMCs) were collected from 53 subjects with primary HIV-1 infection and 31 HIV-1-negative healthy subjects. The percentages of CD56+ T cells and the expression of several phenotypic markers on CD56+ T cells including CD16, CD161, NKB1, NKG2A, NKp46, NKG2D, NKG2C and CD158a were analyzed by flow cytometry. IFN-γ and TNF-α released by CD56+ T cells with and without K562 stimulation and the levels of cytotoxic molecular CD107a were measured. Results The percentages of CD56+ T cells in patients with primary HIV-1 infection were significantly lower than those of healthy subjects (P=0.025). The levels of CD56+ T cells were negatively related to the viral loads in plasma samples (P=0.021, r=-0.316). Compared with healthy subjects, the expression of CD16 (P=0.003), CD161 (P=0.023), NKB1 (P=0.023) and NKp46 (P=0.021) on CD56+ T cells were decreased in patients with primary HIV-1 infection. The levels of NKB1 were positively related to the CD4+ T cell counts (P=0.007, r=0.364), but were negatively related to the viral loads in plasma samples (P=0.030, r=-0.299). Spontaneous secretion of IFN-γ and TNF-α by CD56+ T cells and the expression of CD107a were dramatically inhibited in patients with primary HIV-1 infection as compared with healthy subjects (all P<0.001). Moreover, the killing ability of CD56+ T cells against K562 target cells was weakened in patients with primary HIV-1 infection as the levels of IFN-γ-, TNF-α- and CD107a-producting CD56+ T cells were significantly decreased (P<0.001 for IFN-γ and TNF-α, P=0.016 for CD107a). Conclusion Inhibited expression and altered phenotypes of CD56+ T cells were identified during primary HIV-1 infection. Lower levels of cytokines and cytotoxic molecular were also detected, indicating the dysfunction of CD56+ T cells appeared during early stage of HIV-1 infection and was associated with disease progression. Key words: Human immunodeficiency virus; CD56+ T cells; Phenotype; Cytotoxicity

Reduced NK cell activity and abnormal expression of CCR7 and CXCR1 by NK cells analysis in patients with DOCK8 deficiency

DOCK8-deficiency is an autosomal recessive primary immunodeficiency that is characterized by multiple abnormalities of the immune system, including a defect of NK cell cytotoxicity which could not be restored after IL2 stimulation. Nevertheless, unanswered questions remain regarding how the absence of DOCK8 leads to predisposition for malignancy, viral, fungal, and bacterial infections. To address these questions we have analyzed NK cell phenotype and functions in patients with DOCK8 deficiency. We observed that NK cells derived from five DOCK8-deficient patients displayed dramatically reduced cytotoxicity which was partially restored after IL-2 stimulation. Analysis of activating and inhibitory NK receptors, including KIRs molecules, chemokine receptors and activation markers on gated CD56+cells by cytofluorimetric analysis showed a substantial defect of CCR7 expression by CD56bright NK cells. Noteworthy, we have also detected the expression of NKG2C and of the chemokine receptor CXCR1 on CD56dull NK cells in DOCK8-deficient cells. Because CCR7 expression by NK cells can be induced after cell culture with IL18 we stimulated NK cells from DOCK-8 deficient patients with IL18. Despite unstimulated CD56bright NK cells from DOCK8 patients showed reduced CCR7 expression, we could not detect any increase of CCR7 on CD56 dull and bright NK cells of DOCK8-deficient patients, whereas CCR7 expression on NK cells derived from healthy donors significantly increased from 5% to 17%. Taken together our results suggest that NK cells of DOCK-8 deficient patients show reduced cytotoxicity and abnormal expression of the chemokine receptors CXCR1 and CCR7 suggesting an abnormal recruitment of these cells to secondary lymphoid organs.