Sutmuller M, Baelde H J, Ouellette S, De Heer E, Bruijn J A
Department of Pathology, Leiden University Hospital, The Netherlands.
Immunology. 1998 Sep;95(1):18-25. doi: 10.1046/j.1365-2567.1998.00565.x.
A limited T-cell receptor (TCR) Vbeta repertoire employed by autoreactive T cells may be related to the development and course of autoimmune diseases. Vbeta repertoire skewing has been observed not only in man, but also in animal models of several human autoimmune diseases, such as MRL-lpr mice, which spontaneously develop a systemic lupus erythematosus (SLE)-like disease. Murine chronic graft-versus-host disease (GVHD) is an inducible model for SLE, involving direct interaction between donor T cells and recipient B cells. It is not known whether Vbeta-specific T-cell subsets are pathogenically involved in this model. Retroviral superantigens such as Mls-1 are known to have a profound impact on the TCR Vbeta repertoire in mice. Restriction of the peripheral TCR repertoire may result from intrathymic expression of Mls-1, which causes deletion of T cells expressing Vbeta6, -7, -8.1, or -9. Mls-1 incompatibility between donor and recipient can be used to determine the involvement of these TCR Vbeta families in GVHD. In the present study we induced GVHD in several strain combinations to investigate TCR Vbeta gene expression during GVHD, and the effect of Mls-1 incompatibility on the TCR Vbeta repertoire. TCR Vbeta gene expression was determined using an RNase protection assay. Our results indicate that T cells expressing the Vbeta2 or Vbeta16 chain play an important pathogenetic role, while T cells bearing the Vbeta1 or Vbeta6 chain may be related to self-limitation of the lupus-like disease in this model.
自身反应性T细胞所采用的有限T细胞受体（TCR）Vβ库可能与自身免疫性疾病的发生发展及病程有关。不仅在人类中观察到Vβ库偏移，在几种人类自身免疫性疾病的动物模型中也有发现，如自发发生系统性红斑狼疮（SLE）样疾病的MRL-lpr小鼠。小鼠慢性移植物抗宿主病（GVHD）是SLE的一种诱导模型，涉及供体T细胞与受体B细胞之间的直接相互作用。目前尚不清楚Vβ特异性T细胞亚群是否在该模型中具有致病性。已知逆转录病毒超抗原如Mls-1对小鼠的TCR Vβ库有深远影响。外周TCR库的受限可能源于胸腺内Mls-1的表达，其导致表达Vβ6、-7、-8.1或-9的T细胞缺失。供体与受体之间的Mls-1不相容性可用于确定这些TCR Vβ家族在GVHD中的作用。在本研究中，我们在几种品系组合中诱导GVHD，以研究GVHD期间TCR Vβ基因表达以及Mls-1不相容性对TCR Vβ库的影响。使用核糖核酸酶保护试验确定TCR Vβ基因表达。我们的结果表明，表达Vβ2或Vβ16链的T细胞发挥重要的致病作用，而携带Vβ1或Vβ6链的T细胞可能与该模型中狼疮样疾病的自我限制有关。
