机构地区:[1]中国疾病预防控制中心性病艾滋病预防控制中心,北京102206
出 处:《中华微生物学和免疫学杂志》2015年第3期161-166,共6页Chinese Journal of Microbiology and Immunology
基 金:国家科技重大专项(2012ZX10001008,2014ZX10001001-002);传染病预防控制国家重点实验室项目(2012SKLID103,2011SKLID207)
摘 要:目的探讨HIV-1早期感染者外周血中CD56+T细胞表型和功能变化特点,了解该变化与疾病进展状态的相关性。方法采集HIV-1早期感染者样品53例,HIV-1阴性健康对照31例,分离外周血单个核细胞(PBMC)后,流式细胞术检测CD56+T细胞数量及细胞表面分子CD16、CD161、NKB1、NKG2A、NKp46、NKG2D、NKG2C、CD158a表达水平。将PBMC与K562细胞共孵育,检测CD56+T细胞分泌细胞因子IFN.吖和TNF—d的水平,以及细胞毒效应分子CD107a的水平。结果HIV-1早期感染者外周血中CD56+T细胞数量较健康对照明显减少(P=0.025),且与血浆病毒载量呈负相关(P=0.021,r=-0.316)。CD56+T细胞表面分子CD16(P=0.003)、CD161(P=0.023)、NKBl(P=0.023)、NKp46(P=0.021)表达较健康对照显著降低,其中NKB1的表达水平与CD4+T细胞数量呈正相关(P=0.007,F=0.364),而与病毒载量呈负相关(P=0.030,r=-0.299)。HIV-1早期感染者CD56+T细胞自发分泌IFN-1和TNF-d以及细胞毒效应分子CD107a水平明显低于健康对照(P均〈0.001),在靶细胞K562存在情况下,其杀伤能力也显著低于健康对照(IFN-γ和TNF-α:P均〈0.001,CD107a:JP=0.016)。结论HIV-1早期感染者CD56+T细胞数量下降,表型发生改变,分泌细胞因子和细胞毒效应分子能力下降,提示在HIV-1感染早期CD56’T细胞即受到损伤,且与疾病进展相关。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 in- hibited 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-3,-, 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
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