Highly conserved CDR3 region in circulating CD4(+)Vβ5(+) T cells may be associated with cytotoxic activity in Chagas disease.
Highly conserved CDR3 region in circulating CD4(+)Vβ5(+) T cells may be associated with cytotoxic activity in Chagas disease.
复制标题
循环CD4( )Vβ5( ) T 细胞中高度保守的CDR3 区域可能与恰加斯病的细胞毒活性有关。
DOI：
10.1111/j.1365-2249.2012.04608.x
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发表时间：
2012
影响因子：
4.6
通讯作者：
Dutra,WO
中科院分区：
文献类型：
--
作者：
Menezes,CAS;Sullivan,AK;Falta,MT;Mack,DG;Freed,BM;Rocha,MOC;Gollob,KJ;Fontenot,AP;Dutra,WO
人类感染锥虫可导致恰加斯病，表现为几种不同的临床症状，从无症状到严重的扩张型心肌病。一些研究表明，T细胞在心脏病理的发展中起着关键作用，在慢性疾病中也发挥着免疫调节作用。然而，驱动保护性或致病性T细胞反应的机制尚不清楚。本研究的目的是确定表达T细胞受体β链可变区(V-β)5的T细胞是可变的还是受限的，以此作为在活体中导致这些T细胞被激活的刺激的性质的指标。此外，我们的目的是评估这些细胞的表型特征，可能与病理相关。对表达Vβ5·1的CD4+T细胞的CDR3连接区序列分析显示，在心脏病患者中存在高度同源的CDR3区，而TCRJβ区的使用是保守的。相关分析表明，β5·1+细胞的频率与颗粒酶A的表达有关，提示这些细胞可能具有细胞毒作用。总之，这些结果为T细胞对查格斯病相关抗原的识别提供了新的见解，并提示这些细胞可能与查格斯病心肌病的发病机制有关。
Human infection withTrypanosoma cruzileads to Chagas disease, which presents as several different clinical conditions ranging from an asymptomatic form to a severe dilated cardiomyopathy. Several studies have demonstrated that T cells play a critical role in the development of cardiac pathology, as well as in immunoregulation during chronic disease. However, the mechanisms that drive protective or pathogenic T cell response are not known. We have shown that CD4+T cells from chagasic patients preferentially express T cell receptor (TCR) β-chain variable region (Vβ) 5. The aim of this work was to determine whether T cells expressing this particular Vβ region displayed variable or restricted CDR3 sequences, as an indicator of the nature of the stimulus leading to the activation of these T cellsin vivo.Additionally, we aimed to evaluate phenotypic characteristics of these cells that might be associated with pathology. CDR3 junctional region sequencing of Vβ5·1 expressing CD4+T cells revealed the occurrence of a highly homologous CDR3 region with conserved TCR Jβ region usage among patients with cardiac, but not indeterminate, Chagas disease. Moreover, correlation analysis indicated that the frequency of CD4+Vβ5·1+cells is associated with granzyme A expression, suggesting that these cells might display cytotoxic function. Together these results provide new insight into T cell recognition of antigens involved in Chagas disease and suggest that these cells may be implicated in the pathogenesis of chagasic cardiomyopathy.