T-cell receptor variable region usage in Chagas disease: A systematic review of experimental and human studies.

T-cell receptor variable region usage in Chagas disease: A systematic review of experimental and human studies.
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DOI:
10.1371/journal.pntd.0010546
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发表时间:
2022-09
影响因子:
3.8
通讯作者:
--
中科院分区:
医学2区
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--
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T细胞通过T细胞受体(TCR)识别其配体,即肽类主要组织相容性复合体(MHC),TCR由共价连接的α和β或γ和δ链组成。这种识别对于T细胞个体发育至关重要,并控制T淋巴细胞的选择,活化和功能。特异性TCR αβ可变区与恰加斯病的免疫发病机制有关。在这里,我们提出了一个系统的审查,汇编实验在体内和人体数据的优先表达的可变α(Vα)和可变β(Vβ)链区的克氏锥虫感染。根据PRISMA策略筛选PubMed/Medline、Scopus和Web of Science数据库中索引的原始研究。分析显示,在一项人体研究中评估了TCR Vα亚家族的表达,与TCR Vβ不同,TCR Vα的使用更受限制。尽管在人类查加斯病中TCR Vβ区的使用存在很大的差异,但在疾病急性期患者的T细胞中显示TCR Vβ5表达下调。相反,发现该TCR区域在慢性恰加斯病患者的CD 4 + T细胞中过度表达。小鼠Vβ9+ T细胞来源于T淋巴细胞的非淋巴器官。cruzi感染的动物具有调节特征,而脾Vβ9+ T细胞产生炎性细胞因子,表明尽管它们显示相同的TCR Vβ区用途,但这些细胞在功能上是不同的。尽管论文数量和研究发表年份有限,但汇编从中获得的数据表明,对TCR使用的进一步研究将指出其在保护性或致病性反应中的潜在作用,作为疾病进展的生物标志物,以及寻找可能用于疫苗或疗法开发的优势肽。查加斯病是一种被忽视的热带疾病,由克氏锥虫感染引起。某些T细胞受体(TCR)可变区的差异表达与恰加斯病的免疫发病机制有关。在这里,我们提出了一个系统的审查,汇编实验在体内和人类数据的优先表达的TCR α和β链可变区在恰加斯病。根据PRISMA策略筛选PubMed/Medline、Scopus和Web of Science数据库中索引的原始研究。尽管TCR Vβ在T. cruzi感染后,结果表明,在查加斯病急性期患者的T细胞中存在TCR Vβ5表达的下调。然而,该区域优先由来自慢性恰加斯病患者的CD 4 + T细胞表达。此外,已经证明来自非淋巴器官的鼠Vβ9+ T细胞显示出调节特征,而脾Vβ9+ T细胞产生炎性细胞因子,这表明尽管它们表达相同的TCR Vβ区,但这些细胞在功能上是不同的。关于TCR表达、特异性和功能的信息对疫苗设计具有关键影响。
T cells recognize their ligand, the peptide major histocompatibility complex (MHC), via the T-cell receptor (TCR), which is composed of covalently linked α and β or γ and δ chains. This recognition is critical for T-cell ontogeny and controls the selection, activation, and function of T lymphocytes. Specific TCR αβ variable regions have been associated with immunopathogenesis of Chagas disease. Here, we present a systematic review that compiles experimental in vivo and human data regarding the preferential expression of variable alpha (Vα) and variable beta (Vβ) chain regions in Trypanosoma cruzi infection. The original studies indexed in PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. The analysis showed that expression of TCR Vα subfamilies were evaluated in one human study, and, unlike TCR Vβ, TCR Vα presented a more restricted usage. Despite the great variability in the usage of TCR Vβ regions in human Chagas disease, a down-regulation of TCR Vβ5 expression by T cells from patients in the acute phase of the disease was shown. Opposingly, this TCR region was found overly expressed in CD4+ T cells from chronic Chagas patients. It was also demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs of T. cruzi-infected animals had a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they display the same TCR Vβ region usage, these cells are functionally distinct. Despite the limitations of few papers and year of publication of the studies, compiling the data derived from them reveals that further investigation of TCR usage will point to their potential role in protective or pathogenic responses, as biomarkers of disease progression, and in the search for dominant peptides potentially useful for the development of vaccines or therapies. Chagas disease is a neglected tropical disease, caused by infection with Trypanosoma cruzi. Differential expression of certain T-cell receptor (TCR) variable regions has been associated with the immunopathogenesis of Chagas disease. Here, we present a systematic review that compiled experimental in vivo and human data regarding the preferential expression of TCR alpha and beta chain variable regions in Chagas disease. The original studies indexed in the PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. Despite the great variability in the use of TCR Vβ in T. cruzi infection, the outcomes indicate that there is a down-regulation of TCR Vβ5 expression in T cells from patients in the acute phase of Chagas disease. However, this region is preferentially expressed by CD4+ T cells from chronic Chagas patients. Additionally, it has been demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs displayed a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they express the same TCR Vβ region, these cells are functionally distinct. Information on TCR expression, specificity and function have critical impact on vaccine design.
DOI: 10.1371/journal.pone.0056347
发表时间: 2013
期刊: PloS one
影响因子: 3.7
作者:
Silva GK;Cunha LD;Horta CV;Silva AL;Gutierrez FR;Silva JS;Zamboni DS
通讯作者: Zamboni DS