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首页> 外文期刊>AIDS >Distinct differentiation profiles of HIV-Gag and Nef-specific central memory CD8+ T cells associated with HLA-B57/5801 and virus control.
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Distinct differentiation profiles of HIV-Gag and Nef-specific central memory CD8+ T cells associated with HLA-B57/5801 and virus control.

机译：与HLA-B57 / 5801和病毒控制有关的HIV-Gag和Nef特异性中央记忆CD8 + T细胞的不同分化特征。

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OBJECTIVES: A superior capacity of controlling HIV has been attributed to CD8(+) T cells directed against HIV-Gag compared to Nef, particularly in the context of some protective human leukocyte antigen (HLA) alleles. To further elucidate this protective effect, we compared the multifunctional and differentiation characteristics of CD8(+) T cells specific for HIV-Gag and Nef in HLA-B57/5801-positive and negative nonprogressors. METHODS: A head-to-head comparison of CD8(+) T cells specific for HIV-Gag and Nef frequencies, cytokine production and differentiation was conducted, in 11 HLA-B57/5801 and 11 HLA-B57/5801 HIV-infected individuals selected from a cohort of 53 nonprogressors by using IFN-gamma-ELISpot assay and flow cytometry analysis of intracellular cytokine production and differentiation profile. Correlations with HIV parameters were studied. RESULTS: Frequencies of Gag-specific but not of Nef-specific CD8(+) T cells correlated with peripheral blood mononuclear cell (PBMC)-associated HIV-DNA. The HIV-Gag and Nef-specific CD8(+) T cells did not differ for IL-2 production in either HLA-B57/5801 or HLA-B57/5801 individuals. The IFN-gamma-producing Gag-specific CD8(+) T cells in HLA-B57/5801 individuals significantly differed from their Nef-specific counterparts by displaying higher proportions of central memory CD45RACCR7 cells positive for CD27(+). This differentiation pattern was not observed in HLA-B57/5801 individuals. Only these HLA-B57/5801-positive Gag-specific CD27(+) central memory CD8(+) T cells, but not their Nef-specific counterparts, negatively correlated with cell-associated HIV-DNA. CONCLUSION: HLA-B57/5801 drives a preferential CD27(+) differentiation of central memory CD8(+) T cells directed against HIV-Gag but not Nef that may contribute to the ability of Gag-specific CD8(+) T cells to better control HIV in HLA-B57/5801 nonprogressors.
机译：目的：与Nef相比，归因于针对HIV-Gag的CD8（+）T细胞具有更高的控制HIV能力，尤其是在某些保护性人类白细胞抗原（HLA）等位基因的情况下。为了进一步阐明这种保护作用，我们比较了HLA-B57 / 5801阳性和阴性非进展者中针对HIV-Gag和Nef的CD8（+）T细胞的多功能和分化特征。方法：在11名HLA-B57 / 5801和11名HLA-B57 / 5801感染HIV的个体中进行了针对HIV-Gag和Nef频率，细胞因子产生和分化的CD8（+）T细胞的头对头比较通过使用IFN-γ-ELISpot分析和流式细胞术分析细胞内细胞因子产生和分化情况从53个非进展者队列中选择。研究了与HIV参数的相关性。结果：Gag特异性但不是Nef特异性CD8（+）T细胞的频率与外周血单核细胞（PBMC）相关的HIV-DNA相关。在HLA-B57 / 5801或HLA-B57 / 5801个体中，HIV-Gag和Nef特异性CD8（+）T细胞在IL-2产生方面没有差异。 HLA-B57 / 5801个体中产生IFN-γ的Gag特异性CD8（+）T细胞与Nef特异性对应物显着不同，其表现出较高比例的CD27（+）阳性中央记忆CD45RACCR7细胞。在HLA-B57 / 5801个人中未观察到这种分化模式。只有这些HLA-B57 / 5801阳性Gag特异性CD27（+）中央记忆CD8（+）T细胞，而不是它们的Nef特异性对应物，与细胞相关的HIV-DNA呈负相关。结论：HLA-B57 / 5801驱动针对HIV-Gag的中央记忆CD8（+）T细胞的优先CD27（+）分化，但不能促进Nef，这可能有助于Gag特异性CD8（+）T细胞的功能更好在HLA-B57 / 5801非进展者中控制HIV。

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