POSTNATAL HEMATOGENOUS & INTRATHYMIC T CELL PROGENITORS

尽管胎儿胸腺和胎儿胸腺中T细胞的产生 在辐射或移植中重建胸腺细胞生成 胸腺依赖于骨髓来源的造血细胞 （原胸腺细胞），胸腺也含有内在的T细胞 祖先 造血与内源性的相对作用 在稳态出生后， 胸腺 虽然这个问题长期以来一直受到关注， 我们的初步研究已经确定， 小鼠和部分体BM嵌合体是探索这一点的理想选择 问题：在稳定状态的胸腺中，只有10%的细胞是 90%的内源性胸腺起源;血行性和 内在祖细胞库是彼此独立的。 的 拟议的研究将描述造血和造血干细胞的后代， 出生后稳态胸腺中的固有T细胞祖细胞 并将为表型的推导提供证据， 功能确定的胸腺细胞和外周T细胞亚群 从一个或另一个祖细胞池中分离出来。 我们将调查 这两个祖细胞库对恢复 胸腺在被氢化可的松或肿瘤耗尽后， 诱导萎缩，并通过选择性照射条件下， 不会消耗动物自身的前胸腺细胞。 体内 研究将结合联合收割机多参数流式细胞术和分选， 结合使用选择性裂解确定的T细胞群体， 它们用于迁移研究的选择性标记， 测定。 拟议工作的意义在于， 阐明T细胞亚类的发育谱系， 稳态条件，并将提供有关 当T细胞产生时，不同T细胞祖细胞的反应 已经被类似于那些可能 临床上遇到的人。

Although the generation of T cells in the fetal thymus and the reestablishment of thymocytopoiesis in the irradiated or grafted thymus is dependent on bone marrow-derived hematogenous immigrants (prothymocytes), the thymus also contains intrinsic T cell progenitors. The relative roles of hematogenous vs. intrinsic progenitors has defied investigation in the steady-state postnatal thymus. Although this question has been of long-standing interest, our preliminary studies have established that congenic parabiotic mice and part body BM chimeras are ideal for exploring this problem: in the steady-state thymus, only 10% of cells are of hematogenous and 90% of intrinsic thymic origin; hematogenous and intrinsic progenitor pools are independent of one another. The proposed studies will characterize the progeny of hematogenous and intrinsic T cell progenitors in the steady-state, post-natal thymus and will provide evidence for the derivation of phenotypically and functionally defined subsets of thymocytes and peripheral T cells from one or the other of the progenitor pools. We will investigate the contribution of these two progenitor pools to the recovery of the thymus following its depletion by hydrocortisone- or tumor- induced atrophy, and by selective irradiation under conditions which do not deplete the animal's own prothymocytes. The in vivo studies will combine multi-parameter flow cytometry and sorting in conjunction with selective lysis of defined T cell populations with their selective labeling for migration studies and with functional assays. The significance of the proposed work is that it will clarify the developmental lineages of T cell subclasses under steady-state conditions and will provide information about the response of different T cell progenitors when T cell production has been compromised by conditions comparable to those that may be clinically encountered in humans.