人类免疫缺陷病毒-人类嵌杯样病毒合并感染个体显示功能性黏膜相关不变 T 细胞和滤泡 T 细胞,而与 PD-1 表达无关。

Human Immunodeficiency Virus-Human Pegivirus Coinfected Individuals Display Functional Mucosal-Associated Invariant T Cells and Follicular T Cells Irrespective of PD-1 Expression.

机构信息

Infection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu, Thiruvarur, India.

Laboratory Centre, Xiamen University Malaysia, Sepang, Malaysia.

出版信息

Viral Immunol. 2024 Jun;37(5):240-250. doi: 10.1089/vim.2024.0007. Epub 2024 May 29.

Abstract

Human pegivirus (HPgV) appears to alter the prognosis of HIV disease by modulating T cell homeostasis, chemokine/cytokine production, and T cell activation. In this study, we evaluated if HPgV had any 'favorable' impact on the quantity and quality of T cells in HIV-infected individuals. T cell subsets such as CD4, CD4, and CD8 T cells, CD4 MAIT cells, CD8 MAIT cells, follicular helper T (TFH) cells, and follicular cytotoxic T (TFC) cells were characterized based on the expression of markers associated with immune activation (CD69, ICOS), proliferation (ki67), cytokine production (TNF-α, IFN-γ), and exhaustion (PD-1). HIVHPgV individuals had lower transaminase SGOT (liver) and GGT (biliary) in the plasma than those who were HPgV. HIV/HPgV coinfection was significantly associated with increased absolute CD4 T cell counts. HIVHPgV and HIVHPgV individuals had highly activated T cell subsets with high expression of CD69 and ICOS on bulk CD4 and CD8 T cells, CD4 MAIT cells, CD8 MAIT cells, and CXCR5CD4 T cells and CXCR5CD8 T cells compared with healthy controls. Irrespective of immune activation markers, these cells also displayed higher levels of PD-1 on CD4 T and CD8 T cells . Exploring effector functionality based on mitogen stimulation demonstrated increased cytokine production by CD4 MAIT and CD8 MAIT cells. Decrease in absolute CD4 T cell counts correlated positively with intracellular IFN-γ levels by CD4 T cells, whereas increase of the same correlated negatively with TNF-α in the CD4 T cells of HIVHPgV individuals. HIV/HPgV coinfected individuals display functional CD4 and CD8 MAIT, TFH, and TFC cells irrespective of PD-1 expression.

摘要

人巨细胞病毒(HPgV)似乎通过调节 T 细胞稳态、趋化因子/细胞因子产生和 T 细胞激活来改变 HIV 疾病的预后。在这项研究中,我们评估了 HPgV 是否对 HIV 感染者 T 细胞的数量和质量有任何“有利”影响。T 细胞亚群,如 CD4、CD4 和 CD8 T 细胞、CD4 MAIT 细胞、CD8 MAIT 细胞、滤泡辅助 T(TFH)细胞和滤泡细胞毒性 T(TFC)细胞,根据与免疫激活(CD69、ICOS)、增殖(ki67)、细胞因子产生(TNF-α、IFN-γ)和衰竭(PD-1)相关的标志物表达进行特征描述。与 HPgV 相比,HIV/HPgV 个体的血浆中转氨酶 SGOT(肝脏)和 GGT(胆道)较低。HIV/HPgV 合并感染与绝对 CD4 T 细胞计数增加显著相关。与健康对照组相比,HIV/HPgV 和 HIV/HPgV 个体的 T 细胞亚群具有高度激活的特征,大量 CD4 和 CD8 T 细胞、CD4 MAIT 细胞、CD8 MAIT 细胞和 CXCR5+CD4 T 细胞和 CXCR5+CD8 T 细胞上 CD69 和 ICOS 的表达较高。无论免疫激活标志物如何,这些细胞在 CD4 T 和 CD8 T 细胞上也显示出更高水平的 PD-1。基于有丝分裂原刺激探索效应功能,显示 CD4 MAIT 和 CD8 MAIT 细胞产生更多的细胞因子。绝对 CD4 T 细胞计数的减少与 CD4 T 细胞内 IFN-γ 水平呈正相关,而 HIV/HPgV 个体中 CD4 T 细胞中同一水平的增加与 TNF-α 呈负相关。无论 PD-1 表达如何,HIV/HPgV 合并感染个体均显示出功能性 CD4 和 CD8 MAIT、TFH 和 TFC 细胞。

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