Virus-specific Th17 Cells Are Induced by Human Cytomegalovirus after Renal Transplantation.

IF 3.6 3区 医学 Q2 IMMUNOLOGY
Ravi Dhital, Kaitlyn Flint, Irina Kaptsan, Shweta Hegde, Reem Daloul, Masako Shimamura
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Abstract

CMV infection and Th17 cells are independently associated with increased risk for late allograft loss after renal transplantation. Although CMV-specific Th17 cells are detectable in animal models and nontransplant clinical populations, evidence linking CMV and Th17 cells after renal transplantation remains unclear. This prospective observational study evaluated a cohort of renal transplant recipients during 12 mo posttransplant to assess the presence of CMV-specific Th17 cells in peripheral blood and their relationship to pretransplant CMV serostatus and CMV DNAemia. CMV-specific Th17 cells were identified among CMV serostatus donor (D)+ and/or recipient (R)+ recipients and expanded during both primary (D+/R-) and reactivated (D+/R+, D-/R+) CMV DNAemia. A subset of CMV-specific Th17 cells coexpressed IFN-γ, indicating a Th1/17 phenotype. These Th17 and Th1/17 cells expressed CCR6, CCR5, activation and terminal differentiation markers (CD95, OX40, HLA-DR, CD57), and a central/effector memory phenotype. CMV-specific Th1/17 cells expressed activating/inhibitory receptors (CD57, 4-1BB, CD160, CTLA-4, PD-1) at higher frequencies than Th17 cells. In contrast, staphylococcal enterotoxin B-induced Th17 cells did not expand during CMV DNAemia, did not differ between CMV serostatus groups over time, expressed CCR6, predominantly coexpressed TNF-α, and had lower expression of activating and inhibitory receptors than pp65-specific Th17 and Th1/17 cells. These data show that CMV-specific Th17 cells expand during episodes of CMV DNAemia among renal transplant recipients, and that these virus-specific Th17 and Th1/17 cells have distinct phenotypes from global circulating Th(1)/17 cells. These results suggest a potential proinflammatory pathway by which CMV-induced Th17 cells may contribute to allograft injury, increasing risk for late allograft loss.

肾移植后人类巨细胞病毒会诱发病毒特异性 Th17 细胞
CMV感染和Th17细胞与肾移植后晚期异体移植损失风险的增加有独立的关联。虽然在动物模型和非移植临床人群中可以检测到 CMV 特异性 Th17 细胞,但肾移植后 CMV 和 Th17 细胞之间的联系仍不明确。这项前瞻性观察研究评估了一组移植后 12 个月的肾移植受者,以评估外周血中 CMV 特异性 Th17 细胞的存在及其与移植前 CMV 血清状态和 CMV DNA 血症的关系。在CMV血清状态为供体(D)+和/或受体(R)+的受者中发现了CMV特异性Th17细胞,并在原发性(D+/R-)和再激活(D+/R+、D-/R+)CMV DNA血症期间扩增。CMV 特异性 Th17 细胞的一个亚群共表达 IFN-γ,表明其表型为 Th1/17。这些Th17和Th1/17细胞表达CCR6、CCR5、活化和终末分化标记(CD95、OX40、HLA-DR、CD57)以及中枢/效应记忆表型。CMV 特异性 Th1/17 细胞表达激活/抑制受体(CD57、4-1BB、CD160、CTLA-4、PD-1)的频率高于 Th17 细胞。与此相反,葡萄球菌肠毒素 B 诱导的 Th17 细胞在 CMV DNA 血症期间没有扩增,在 CMV 血清状态组间没有时间差异,与 pp65 特异性 Th17 细胞和 Th1/17 细胞相比,它们表达 CCR6,主要共表达 TNF-α,活化受体和抑制受体的表达较低。这些数据表明,在肾移植受者发生CMV DNA血症期间,CMV特异性Th17细胞会扩增,而且这些病毒特异性Th17和Th1/17细胞的表型与全球循环中的Th(1)/17细胞不同。这些结果表明,CMV诱导的Th17细胞可能是一种潜在的促炎途径,它可能会导致同种异体移植物损伤,增加晚期同种异体移植物丢失的风险。
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来源期刊
Journal of immunology
Journal of immunology 医学-免疫学
CiteScore
8.20
自引率
2.30%
发文量
495
审稿时长
1 months
期刊介绍: The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)
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