Goldman Kissinger P, Park Chan-Sik, Kim Moon, Matzinger Polly, Anderson Colin C
Ghost Lab, LCMI, NIAID, NIH, Bethesda, MD, USA.
Eur J Immunol. 2005 Mar;35(3):709-17. doi: 10.1002/eji.200425675.
Because of its role in positive selection, the ability of cortical epithelium to induce tolerance is controversial. On the one hand, experiments with transplanted thymuses showed that the recipients were functionally tolerant of all the antigens expressed by the cells of those thymuses, including cells of the cortical epithelium. On the other, the keratin 14 (K14) transgenic mouse strain, which expresses MHC class II on cortical epithelium under the control of the K14 promoter, does not seem to be tolerant of the transgenic MHC molecule. Here we tested whether the lack of tolerance in the K14 mouse might be more apparent than real. We found that K14 mice are indeed completely tolerant of K14 cortical thymic epithelium, whereas they remain reactive to tissues that express the same MHC allele under normal genetic control. These results establish the ability of cortical epithelium to induce central tolerance, and impinge on several of the models concerning positive selection of newly developing T cells.
由于其在阳性选择中的作用，皮质上皮诱导耐受的能力存在争议。一方面，胸腺移植实验表明，受体对那些胸腺细胞所表达的所有抗原，包括皮质上皮细胞的抗原，在功能上具有耐受性。另一方面，在角蛋白14（K14）启动子控制下在皮质上皮表达II类主要组织相容性复合体（MHC）的K14转基因小鼠品系，似乎对转基因MHC分子不耐受。在这里，我们测试了K14小鼠中耐受性的缺乏是否可能比实际情况更明显。我们发现，K14小鼠确实对K14皮质胸腺上皮完全耐受，而它们对在正常遗传控制下表达相同MHC等位基因的组织仍有反应。这些结果证实了皮质上皮诱导中枢耐受的能力，并对有关新发育T细胞阳性选择的几种模型产生影响。
