CD69 expression discriminates MHC-dependent and -independent stages of thymocyte positive selection.
CD69 expression discriminates MHC-dependent and -independent stages of thymocyte positive selection.
复制标题
DOI：
10.4049/jimmunol.162.7.3978
复制
发表时间：
1999-04
影响因子：
4.4
通讯作者：
K. Hare;E. Jenkinson;G. Anderson
中科院分区：
文献类型：
--
作者：
K. Hare;E. Jenkinson;G. Anderson
在胸腺中，表型和功能成熟的单个阳性细胞通过称为阳性选择的过程从未成熟的CD 4 +8+前体产生。尽管已知该事件涉及胸腺基质细胞上表达的肽/MHC复合物的字母顺序TCR连接，但很明显，阳性选择是一个多阶段过程，涉及过渡到中间CD 4 +8+69+阶段以及随后的选择后阶段。通过分析预选CD 4 +8+69-和中间CD 4 +8+69+胸腺细胞在MHC I类缺陷，MHC II类缺陷，和MHC双缺陷的胸腺基质细胞的存在下的发展，我们研究了MHC分子在三个不同的点在积极的选择过程中的作用。虽然阳性选择的启动是严重依赖于MHC的相互作用，我们发现，成熟的后期阶段，涉及从CD 4 +8+69+胸腺细胞分化的CD 4 +8-和CD 4 -8+细胞，发生在没有MHC分子。此外，新产生的CD 4 +8-和CD 4 -8+胸腺细胞的选择后增殖的分析表明，这也发生独立的MHC分子。因此，我们的数据提供了直接的证据，虽然积极的选择是一个多阶段的过程发起的TCR-MHC的相互作用，这个过程的延续和随后的选择后事件是独立的持续参与的TCR。
In the thymus, phenotypically and functionally mature single positive cells are generated from immature CD4+8+ precursors by a process known as positive selection. Although this event is known to involve alphabetaTCR ligation by peptide/MHC complexes expressed on thymic stromal cells, it is clear that positive selection is a multistage process involving transition through an intermediate CD4+8+69+ phase as well as subsequent postselection phases. By analyzing the development of preselection CD4+8+69- and intermediate CD4+8+69+ thymocytes in the presence of MHC class I-deficient, MHC class II-deficient, and MHC double-deficient thymic stromal cells, we investigated the role of MHC molecules at three distinct points during positive selection. Although the initiation of positive selection is critically dependent upon MHC interactions, we find the that later stages of maturation, involving the differentiation of CD4+8- and CD4-8+ cells from CD4+8+69+ thymocytes, occur in the absence of MHC molecules. Moreover, an analysis of the postselection proliferation of newly generated CD4+8- and CD4-8+ thymocytes shows that this also occurs independently of MHC molecules. Thus, our data provide direct evidence that, although positive selection is a multistage process initiated by TCR-MHC interactions, continuation of this process and subsequent postselection events are independent of ongoing engagement of the TCR.