Fukushi N, Wang B Y, Arase H, Ogasawara K, Good R A, Onoé K
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Eur J Immunol. 1990 May;20(5):1153-60. doi: 10.1002/eji.1830200531.
T cells become tolerant to self antigens during their development in the thymus. Clonal deletion of thymocytes bearing T cell receptor (TcR) which recognize self antigens is a major mechanism for generating tolerance. In the present study we have used allogeneic bone marrow (BM) chimeras, prepared with various combinations of mouse strains and focusing especially on expressions of I-E molecules and Mls-1a antigens on the cell surface, to investigate both immunohistochemically and by flow cytometry the cell components that contribute to the clonal deletion of T cells positive for V beta 6 TcR. The V beta 6 TcR expression is strongly associated with T cell recognition of both I-E and Mls-1a antigens. We found that I-E+ cells derived from donor BM (and thus not of recipient lineage) represented a primary requirement for deletion of Mls-1a-reactive thymocytes which bear V beta 6 TcR. Immunohistochemical analysis revealed that the donor-derived I-E+ cells were distributed mainly to the thymic medulla and that the V beta 6+ cells were eliminated from the thymic medulla between 2 and 3 weeks following BM transplantation. In contrast, Mls-1a+ cells of either donor or recipient origin might be responsible for the deletion, even though cortical epithelial cells appeared not to express Mls-1a antigens.
T细胞在胸腺发育过程中对自身抗原产生耐受。带有识别自身抗原的T细胞受体（TcR）的胸腺细胞的克隆清除是产生耐受的主要机制。在本研究中，我们使用了同种异体骨髓（BM）嵌合体，通过不同小鼠品系的各种组合制备，特别关注细胞表面I-E分子和Mls-1a抗原的表达，以通过免疫组织化学和流式细胞术研究促成Vβ6 TcR阳性T细胞克隆清除的细胞成分。Vβ6 TcR表达与T细胞对I-E和Mls-1a抗原的识别密切相关。我们发现，源自供体骨髓的I-E+细胞（因此不是受体谱系的细胞）是清除带有Vβ6 TcR的Mls-1a反应性胸腺细胞的主要条件。免疫组织化学分析显示，供体来源的I-E+细胞主要分布在胸腺髓质，并且在骨髓移植后2至3周内，Vβ6+细胞从胸腺髓质中被清除。相比之下，供体或受体来源的Mls-1a+细胞可能是导致清除的原因，尽管皮质上皮细胞似乎不表达Mls-1a抗原。
