TOLERANCE INDUCTION AS A MULTISTEP PROCESS
TOLERANCE INDUCTION AS A MULTISTEP PROCESS
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DOI：
10.1002/eji.1830240202
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发表时间：
1994-02-01
影响因子：
5.4
通讯作者：
ARNOLD, B
中科院分区：
文献类型：
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作者：
SCHONRICH, G;ALFERINK, J;ARNOLD, B
耐受性 T 细胞的特点是对抗原激活具有部分或完全抵抗力。我们研究了耐受性 T 细胞是否仍能接受进一步的耐受性信号。在携带 Kb 的小鼠中，表达对主要组织相容性复合物 (MHC) I 类分子 Kb 特异的转基因 T 细胞受体 (TCR) 的 T 细胞被删除，但在表达突变型 Kb 分子 K-bm1 [TCR (H-2(bm1xk)) 小鼠]的患病小鼠中则没有。这些 T 细胞在体内具有耐受性，但在体外可以被 Kb 抗原激活。当耐受性 T 细胞遇到静脉注射的 Kb 阳性细胞后，这种体外反应性被消除。此外，在仅在肝细胞上表达Kb的TCR（H-2（bm1xk））小鼠中，在外周未发现带有转基因TCR的T淋巴细胞，这表明与肝细胞上Kb的额外接触导致了耐受性T细胞的缺失。这些发现表明耐受诱导可以是一个多步骤的过程。
Tolerant T cells are characterized by their partial or full resistance to activation by antigen. We investigated whether tolerant T cells were still receptive to further tolerogenic signals. T cells expressing a transgenic T cell receptor (TCR) specific for the major histocompatibility complex (MHC) class I molecule Kb were deleted in mice carrying Kb but not ill mice expressing the mutant Kb-molecule K-bm1 [TCR (H-2(bm1xk)) mice]. These T cells were tolerant in vivo but could be activated in vitro by the Kb antigen. This in vitro reactivity was abolished after the tolerant T cells encountered Kb-positive cells that had been intravenously injected. Furthermore, in TCR (H-2(bm1xk)) mice expressing Kb only on hepatocytes, no T lymphocytes bearing the transgenic TCR could be found in the periphery, indicating that the additional contact with Kb on hepatocytes led to deletion of the tolerant T cells. These findings demonstrate that tolerance induction can be a multi-step process.