TOLERANCE INDUCTION IN DOUBLE SPECIFIC T-CELL RECEPTOR TRANSGENIC MICE VARIES WITH ANTIGEN
TOLERANCE INDUCTION IN DOUBLE SPECIFIC T-CELL RECEPTOR TRANSGENIC MICE VARIES WITH ANTIGEN
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DOI：
10.1038/342559a0
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发表时间：
1989-11-30
期刊：
影响因子：
64.8
通讯作者：
ZINKERNAGEL, RM
中科院分区：
文献类型：
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作者：
PIRCHER, H;BURKI, K;ZINKERNAGEL, RM
胸腺在免疫耐受中的关键作用1 - 5已经通过以下事实得到证实：T细胞被积极选择以表达对自身主要组织相容性复合体（MHC）的特异性6-8，而那些携带对自身抗原片段（可能由胸腺MHC呈递）潜在反应性受体的T细胞被选择对抗9 -11。诱导耐受性的确切机制和发生耐受性的T细胞发育阶段尚不清楚。我们现在已经研究了T细胞耐受性的转基因小鼠表达的T细胞受体的淋巴细胞脉络丛脑膜炎病毒（LCMV）-H-2D带的混合淋巴细胞刺激（Mlsa）抗原的双重特异性。我们报道了对LCMV耐受的αβTCR转基因小鼠的CD 4 + CD 8+胸腺细胞和携带CD 8抗原的外周T细胞的数量显著减少。相比之下，相同αβTCR转基因Mlsamice中对Mlsa抗原的耐受性仅导致成熟胸腺细胞和外周T细胞的缺失，并且不影响CD 4 + CD 8+胸腺细胞。因此，根据所涉及的抗原，相同的转基因TCR表达T细胞可以在其成熟的不同阶段和在胸腺中的不同位置被耐受。
THE crucial role of the thymus in immunological tolerance1–5has been demonstrated by establishing that T cells are positively selected to express a specificity for self major histocompatibility complex (MHC)6–8, and that those T cells bearing receptors potentially reactive to self antigen fragments, presumably presented by thymic MHC, are selected against9–11. The precise mechanism by which tolerance is induced and the stage of T-cell development at which it occurs are not known. We have now studied T-cell tolerance in transgenic mice expressing a T-cell receptor with double specificities for lymphocytic choriomeningitis virus (LCMV)-H-2Dband for the mixed-lymphocyte stimulatory (Mlsa) antigen. We report that αβTCR transgenic mice tolerant to LCMV have drastically reduced numbers of CD4+CD8+thymocytes and of peripheral T cells carrying the CD8 antigen. By contrast, tolerance to Mlsaantigen in the same αβTCR transgenic Mlsamice leads to deletion of only mature thymocytes and peripheral T cells and does not affect CD4+CD8+thymocytes. Thus the same transgenic TCR-expressing T cells may be tolerized at different stages of their maturation and at different locations in the thymus depending on the antigen involved.