HIV-1早期感染者外周血中 CD56＋T细胞表型和功能特征分析

摘要

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-γand TNF-αreleased 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).Sponta-neous secretion of IFN-γand TNF-αby 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 prima-ry 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-γand 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 cy-tokines and cytotoxic molecular were also detected, indicating the dysfunction of CD56+T cells appeared dur-ing early stage of HIV-1 infection and was associated with disease progression.%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-γ和TNF-α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）、NKB1（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，r＝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-γ和TNF-α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：P＝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。