Saurer Leslie, Seibold Inge, Vallan Claudio, Held Werner, Mueller Christoph
Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland.
J Immunol. 2003 Dec 15;171(12):6334-8. doi: 10.4049/jimmunol.171.12.6334.
NK cell self-tolerance is maintained by inhibitory receptors specific for MHC class I molecules. Inhibitory NK receptors are also expressed on memory CD8 T cells but their biological relevance on T cells is unclear. In this study, we describe the expression of the Ly49A receptor on a subset of autoreactive T cells which persist in mice double-transgenic for the lymphocytic choriomeningitis virus-derived peptide gp33 and a TCRalphabeta specific for the gp33. No Ly49A-expressing cells are found in TCRalphabeta single-transgenic mice, indicating that the presence of the autoantigen is required for Ly49A induction. Direct evidence for an Ag-specific initiation of Ly49A expression has been obtained in vitro after stimulation of autoreactive TCRalphabeta T cells with the cognate self-Ag. This expression of Ly49A substantially reduces Ag-specific activation of autoreactive T cells. These findings thus suggest that autoantigen-specific induction of inhibitory NK cell receptors on T cells may contribute to peripheral self-tolerance.
NK细胞的自身耐受性由对MHC I类分子特异的抑制性受体维持。抑制性NK受体也在记忆性CD8 T细胞上表达，但其在T细胞上的生物学相关性尚不清楚。在本研究中，我们描述了Ly49A受体在一部分自身反应性T细胞上的表达，这些细胞存在于淋巴细胞性脉络丛脑膜炎病毒衍生肽gp33和对gp33特异的TCRαβ双转基因小鼠中。在TCRαβ单转基因小鼠中未发现表达Ly49A的细胞，这表明自身抗原的存在是Ly49A诱导所必需的。在用同源自身抗原刺激自身反应性TCRαβ T细胞后，已在体外获得了Ly49A表达的抗原特异性起始的直接证据。Ly49A的这种表达显著降低了自身反应性T细胞的抗原特异性激活。因此，这些发现表明T细胞上抑制性NK细胞受体的自身抗原特异性诱导可能有助于外周自身耐受性。
