Rao N A, Naidu Y M, Bell R, Lindsey J W, Pararajasegaram G, Sun Y, Steinman L
Doheny Eye Institute, Los Angeles, CA 90033.
J Immunol. 1993 Jun 15;150(12):5716-21.
Improved molecular methods allow identification of the specific autoaggressive T cells involved in autoimmune inflammations. In this study of interphotoreceptor retinoid-binding protein-induced uveitis, TCR V beta usage was studied using RNA-polymerase chain reaction amplification of transcripts derived directly from ocular tissues and from T cell lines obtained from the spleen. Specific V beta 5' primers from the major murine TCR V beta families were coupled with a common 3' primer from the V beta C region. Amplification of rearranged TCR V beta-D beta-J beta-C beta sequences was confirmed by Southern blot analysis. In ocular tissue from sensitized mice, TCR V beta expression was limited mainly to one to three V beta families, with predominant expression of V beta 2, V beta 12, and V beta 15. In most animals there was similar, albeit limited, TCR gene usage in both the recognition of autoantigen in uveitogenic T cell lines and at the site of inflammation in the eye. Identification of a limited TCR V beta repertoire in Ag-reactive T cell lines correlated with TCR usage at the target site of autoimmune expression. The gene products of the restricted TCR V beta rearrangements found in lesions and in the cell lines may serve as the target for selective immunotherapy.
改进的分子方法能够鉴定参与自身免疫性炎症的特定自身攻击性T细胞。在这项关于光感受器间类视黄醇结合蛋白诱导的葡萄膜炎的研究中，通过对直接从眼组织和从脾脏获得的T细胞系中提取的转录本进行RNA聚合酶链反应扩增，研究了TCR Vβ的使用情况。来自主要小鼠TCR Vβ家族的特异性Vβ 5'引物与来自Vβ C区域的通用3'引物相结合。通过Southern印迹分析证实了重排的TCR Vβ-Dβ-Jβ-Cβ序列的扩增。在致敏小鼠的眼组织中，TCR Vβ表达主要局限于一到三个Vβ家族，其中Vβ 2、Vβ 12和Vβ 15表达占主导。在大多数动物中，在致葡萄膜炎性T细胞系中自身抗原的识别以及在眼部炎症部位，TCR基因的使用情况相似，尽管有限。在Ag反应性T细胞系中有限的TCR Vβ库的鉴定与自身免疫表达靶位点的TCR使用情况相关。在病变部位和细胞系中发现的受限TCR Vβ重排的基因产物可能成为选择性免疫治疗的靶点。
