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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ontogeny of T cell tolerance to peripherally expressed antigens
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Ontogeny of T cell tolerance to peripherally expressed antigens

机译：T细胞对外周表达抗原的耐受性

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Transgenic expression of the influenza virus hemagglutinin (HA) in the pancreatic islet beta cells of InsHA mice leads to Peripheral tolerance of HA-specific T cells. To examine the onset of tolerance, InsHA mice were immunized with influenza virus A/PR/8 at different ages, and the pres- ence of nontolerant T cells was determined by the induction of autoimmune diabetes. The data revealed a neonatal period wherein T cells were not tolerant and influenza virus infection led to HA-specific p cell destruction and autoimmune diabe- tes. The ability to induce autoimmunity gradually waned, such that adult mice were profoundly tolerant to viral HA and were protected from diabetes. Because cross-presentation of islet antigens by professional antigen-presenting cells had been reported to induce peripheral tolerance, the temporal rela- tionship between tolerance induction and activation of HA- specific T cells in the Iymph nodes draining the pancreas was examined. In tolerant adult mice, but not in 1-week-old neonates, activation and proliferation of HA-specific CD8+ T cells occurred in the pancreatic lymph nodes. Thus, Iack of tolerance in the perinatal period correlated with lack of activation of antigen-specific CD8+ T cells. This work provides evidence for the developmental regulation of peripheral tol- erance induction.
机译：流感病毒血凝素（HA）在InsHA小鼠的胰岛β细胞中的转基因表达导致HA特异性T细胞的外周耐受。为了检测耐受性的发作，用不同年龄的流感病毒A / PR / 8对InsHA小鼠进行免疫，并通过诱导自身免疫性糖尿病来确定非耐受性T细胞的存在。数据表明，新生儿时期不耐受T细胞，流感病毒感染导致HA特异性p细胞破坏和自身免疫性糖尿病。诱导自身免疫的能力逐渐减弱，以至于成年小鼠对病毒HA的耐受力极强，并且可以预防糖尿病。由于据报道，专业抗原呈递细胞对胰岛抗原的交叉呈递可诱导外周耐受，因此，我们研究了胰岛引流淋巴结中耐受诱导与HA特异性T细胞活化之间的时间关系。在耐受的成年小鼠中，但在1周龄的新生儿中则没有，在胰腺淋巴结中发生HA特异性CD8 + T细胞的活化和增殖。因此，围产期缺乏耐受性与缺乏抗原特异性CD8 + T细胞的激活有关。这项工作为周围耐受诱导的发展调控提供了证据。

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