Arenz M, Herzog-Hauff S, Meyer zum Büschenfelde K H, Löhr H F
I. Department of Internal Medicine, University of Mainz, Germany.
J Mol Med (Berl). 1997 Sep;75(9):678-86. doi: 10.1007/s001090050152.
Analysis of the variable chains (V alpha/V beta) of the specific T cell receptor (TCR) of organ-infiltrating T cells may provide further insights into the pathogenesis of many infectious diseases, malignancies, and autoimmune disorders. To determine the TCR V beta repertoire of these small T cell populations antigen-independent in vitro expansion is necessary but may select for certain T cell subpopulations. In this study various antigen independent T cell activation protocols were used to stimulate peripheral blood mononuclear cells (PBMC) of six healthy blood donors, and TCR V beta molecules were analyzed by flow cytometry and semiquantitative reverse-transcriptase polymerase chain reaction. In addition, the analysis of in vitro expanded liver-infiltrating T cells and autologous peripheral blood T cells derived from five patients with autoimmune hepatitis but none of six controls revealed a selective overexpression of single TCR V beta molecules in the liver tissue. In contrast to freshly isolated PBMC, no preferential expansion of single TCR V beta families was observed using phytohemagglutinin, anti-CD3 antibodies, or oxidative stress for antigen-independent T cell activation. In conclusion, antigen-independent T cell activation offers the chance to analyze small populations of organ-infiltrating T cells without skewing the TCR V beta repertoire.
分析器官浸润性T细胞特异性T细胞受体(TCR)的可变链(Vα/Vβ),可能会为许多传染病、恶性肿瘤和自身免疫性疾病的发病机制提供进一步的见解。为了确定这些小T细胞群体的TCR Vβ库,体外抗原非依赖性扩增是必要的,但可能会选择某些T细胞亚群。在本研究中,使用了各种抗原非依赖性T细胞激活方案来刺激6名健康献血者的外周血单核细胞(PBMC),并通过流式细胞术和半定量逆转录聚合酶链反应分析TCR Vβ分子。此外,对来自5例自身免疫性肝炎患者而非6例对照的体外扩增肝浸润性T细胞和自体外周血T细胞的分析显示,肝组织中单个TCR Vβ分子有选择性的过表达。与新鲜分离的PBMC不同,使用植物血凝素、抗CD3抗体或氧化应激进行抗原非依赖性T细胞激活时,未观察到单个TCR Vβ家族的优先扩增。总之,抗原非依赖性T细胞激活为分析器官浸润性T细胞的小群体提供了机会,而不会扭曲TCR Vβ库。