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高表达 CD300a 的 CD8+ T 淋巴细胞的多功能性 HIV-1 特异性反应。

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a.

机构信息

Biocruces Bizkaia Health Research Institute, Immunopathology Group, 48903, Barakaldo, Spain.

Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, University of Seville, CSIC, 41013, Seville, Spain.

出版信息

Sci Rep. 2020 Apr 8;10(1):6070. doi: 10.1038/s41598-020-63025-4.

DOI:10.1038/s41598-020-63025-4
PMID:32269232
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7142067/
Abstract

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)-1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a Gag HIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response.

摘要

CD300a 受体存在于不同的 CD8+T 细胞亚群上,其表达与更具细胞毒性的分子特征相关。CD300a 在某些病毒感染中具有重要作用,其表达水平已知可被人类免疫缺陷病毒(HIV)-1 感染多种细胞类型所调节。这项工作的主要目的是研究 HIV-1 特异性 CD8+T 细胞反应过程中 CD300a 的表达及其调控。通过多参数流式细胞术分析来自 HIV 阴性供体、未感染 HIV-1 的个体和接受抑制性联合抗逆转录病毒治疗(cART)的 HIV-1 阳性个体的 CD8+T 淋巴细胞上的 CD300a 受体表达。通过用 HIV-1 衍生肽或 Gag HIV-1 肽刺激细胞来研究 HIV-1 特异性 CD8+T 细胞反应。我们的结果表明,表达更高水平 CD300a 的 HIV-1 特异性 CD8+T 细胞具有更高的多功能性,表现为脱颗粒和细胞因子产生增加。此外,我们观察到 Gag HIV-1 肽刺激后 CD300a 表达上调。最后,我们的结果表明 CD300a 表达与 HIV 疾病进展标志物呈负相关。总之,CD300a 表达与更好和更具多功能性的 HIV-1 特异性 CD8+T 细胞反应相关。

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