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早期HIV-1感染者KIR3 DL1阳性CD8细胞表型和功能的探索研究

Phenotypes and HIV-1-specific T cell responses of KIR3DL1 positive CD8 cells in patients with early HIV-1 infection

摘要目的:探讨 KIR3DL1受体在早期 HIV-1感染者 CD8细胞亚群的表达特点和KIR3DL1+CD8+细胞HIV-1特异性应答能力。方法用流式细胞术检测56例HIV-1阴性对照者和32例早期HIV-1感染者的CD8细胞亚群;同时用HIV-1 Gag多肽库刺激HIV-1感染者的外周血单个核细胞( PBMCs),用胞内细胞因子染色技术检测CD8细胞分泌IFN-γ水平。结果 HIV-1阴性对照者和HIV-1感染者CD8细胞中KIR3DL1+CD8+细胞比例的中位数分别为1.45%(0.12%~8.4%)和0.82%(0.14%~6.14%),差异无统计学意义。 KIR3DL1受体在HIV-1阴性者和HIV-1感染者CD8终端效应细胞的表达比例平均值分别是(4.55±3.84)%和(6.71±8.50)%,显著高于在CD8效应记忆细胞的表达比例,其平均值分别是(0.50±0.59)%和(1.18±1.39)%(P<0.001)。而且,早期HIV-1感染者CD8效应记忆细胞中KIR3DL1阳性细胞比例显著高于HIV-1阴性者(P=0.0012)。早期HIV-1感染者的KIR3DL1+CD8+终端效应细胞比例与HIV-1载量呈正比(rs=0.576,P=0.0009);而且,HIV-1载量≤4.0log 的 HIV-1感染者 KIR3DL1+CD8+终端效应细胞的比例显著小于病毒载量>4.0log的感染者(P=0.002)。 HIV-1感染者KIR3DL1+CD8+细胞诱导产生HIV-1-特异性IFN-γ的水平远低于KIR3DL1-CD8+细胞。结论 KIR3DL1受体主要表达在CD8终端效应细胞,HIV-1病毒血症高时KIR3DL1受体在终端效应细胞的表达比例高;表达 KIR3DL1受体的 CD8细胞诱导产生的HIV-1特异性T细胞的应答能力低。

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abstractsObjective To investigate the phenotypes and the HIV-1-specific T cell responses of KIR3DL1 positive CD8 cells in patients with early HIV-1 infection. Methods Fifty-six HIV-1 antibody negative individuals and thirty-two patients with early HIV-1 infection were enrolled in the study. Fluores-cence-activated cell sorting (FACS) was performed to detect the phenotypes of KIR3DL1 receptor expressed on the surface of CD8 cells. The levels of IFN-γwere measured by intracellular cytokine staining assay after the PBMCs were stimulated with an HIV-1 Gag peptide pool. Results The percentages of KIR3DL1+CD8 T cells in HIV-1 negative individuals and patients with early HIV-1 infection were 1. 45% (0. 12%-8. 4%) and 0. 82% (0. 14%-6. 14%), respectively, and there was no significant difference between them. The percentages of KIR3DL1+CD8 Temra cells in HIV-1 negative individuals and patients with early HIV-1 infec-tion were (4. 55±3. 84)% and (6. 71±8. 50)%, respectively, which were significantly higher than the per-centages of KIR3DL1+CD8 Tem cells, which were (0. 50±0. 59)% and (1. 18±1. 39)%, respectively (all P<0. 01). Moreover, the percentages of KIR3DL1+CD8 Tem cells in patients with early HIV-1 infection&nbsp;were higher than those in HIV-1 negative individuals (P=0. 001 2). The percentage of KIR3DL1+CD8 Temra cells was positively correlated with the HIV-1 viral load in patients with early HIV-1 infection ( rs=0. 576,P=0. 000 9). The percentages of KIR3DL1+CD8 Temra cells in HIV-1 patients, whose viral loads were larger than 4. 0log, were much higher than those in HIV-1 patients with viral loads less than 4. 0 log (P=0. 002). Additionally, the levels of IFN-γsecreted by KIR3DL1 positive CD8 cells were much lesser than those secreted by KIR3DL1 negative CD8 cells (P<0. 000 1). Conclusion The receptor of KIR3DL1 was mainly expressed on CD8 Temra cells in both HIV-1 negative subjects and patients with early HIV-1 infec-tion. High HIV-1 viremia was associated with the high percentage of KIR3DL1+CD8 Temra cells. The KIR3DL1 positive CD8 cells induced lower HIV-1-specific T cell responses.

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