Schönrich G, Alferink J, Klevenz A, Küblbeck G, Auphan N, Schmitt-Verhulst A M, Hämmerling G J, Arnold B
Tumor Immunology Program, German Cancer Research Center, Heidelberg.
Eur J Immunol. 1994 Feb;24(2):285-93. doi: 10.1002/eji.1830240202.
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 in mice expressing the mutant Kb-molecule Kbm1 [TCR (H-2bm1 x k) 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-2bm1 x k) 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.
耐受型T细胞的特征在于它们对抗原激活具有部分或完全抗性。我们研究了耐受型T细胞是否仍能接受进一步的致耐受性信号。在携带Kb的小鼠中，表达对主要组织相容性复合体（MHC）I类分子Kb具有特异性的转基因T细胞受体（TCR）的T细胞被删除，但在表达突变型Kb分子Kbm1的小鼠[ TCR（H-2bm1 x k）小鼠]中未被删除。这些T细胞在体内呈耐受状态，但在体外可被Kb抗原激活。在耐受型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-2bm1 x k）小鼠中，在外周血中未发现携带转基因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型T细胞的删除。这些发现表明，耐受性诱导可能是一个多步骤过程。
