GENE REGULATORY EVENTS IN T CELL TOLERANCE AND THYMIC T CELL MATURATION

越来越多的证据表明T细胞成熟中的重要事件， 胸腺和耐受诱导受特定基因控制 调控已经发现T细胞耐受发生在未成熟的T细胞中 在胸腺和胸腺外成熟T细胞中。我们的研究 成熟T细胞无应答性表明IL-2表达 基因通过下调细胞原癌基因而失能， 形成AP-1基因活化复合物的一部分。 胸腺外缺失 成熟的T细胞也涉及IIL-2，它被发现可以编程 这些细胞在抗原受体占据后死亡。 在胸腺中，前体细胞经历一系列复杂的发育过程， 事件，并作为成熟的T淋巴细胞出现，能够特异性抗原 识别. 我们发现，基因表达在不同的 胸腺发育的各个阶段在各种转化细胞系中， 代表了胸腺发育的不同阶段 我们专注于 IL-2及其受体α和β链的基因调控。 我们也在试图鉴定与克隆性疾病相关的基因产物， 胸腺中的缺失。 最后，我们试图理解 基因，特别是细胞原癌基因，在肿瘤的进展中， 胸腺细胞通过其成熟途径。

Increasing evidence suggests important events in T cell maturation in the thymus and tolerance induction are governed by specific gene regulation. T cell tolerance has been found to occur in immature T cells in the thymus and also extrathymically in mature T cells. Our studies of mature T cell non-responsiveness have shown that expression of the IL-2 gene is disabled by down-regulation of a cellular proto-oncogene that forms part of the AP-1 gene activation complex. Extra-thymic deletion of mature T cells also involves IIL-2 which has been found to program these cells for death following antigen receptor occupancy. In the thymus, precursor cells undergo a complex set of developmental events and emerge as mature T lymphocytes capable of specific antigen recognition. We have found that gene expression varies at different stages of thymic development in a variety of transformed cell lines that represent discrete stages of thymic development. We are focusing on regulation of the genes for IL-2 and its receptor alpha and beta chains. We are also trying to identify gene products associated with clonal deletion in the thymus. Finally we are trying to understand the role of genes, especially cellular proto-oncogenes, in the progression of thymocytes through their maturation pathway.