Dyall R, Nikolić-Zugić J
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York 10021.
J Exp Med. 1995 Jan 1;181(1):235-45. doi: 10.1084/jem.181.1.235.
We have previously isolated, and characterized in vitro, two subsets of CD4hi T cell receptor (TCR)hi single positive (SP) thymocytes: CD8- and CD8lo. In this report, we have analyzed phenotypic, functional, and developmental characteristics of these "late" CD4hi SP thymocyte subsets. The TCRhi phenotype and the elimination of T cells expressing TCR V beta segments reactive with endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets had undergone positive and negative selection. CD8-4hi thymocytes were functional, as judged by their ability to: (a) induce lethal graft versus host disease (GVHD); (b) survive and expand in peripheral lymphoid organs; and (c) proliferate, rather than undergo apoptosis, in response to in vitro TCR cross-linking. By contrast, CD8lo4hi cells could not induce GVHD, were unable to expand (and perhaps even survive) in peripheral organs and underwent apoptosis upon TCR cross-linking. However, when reintroduced into the thymus, these cells matured into functional, long-lived CD8-4hi lymphocytes. These results document an obligatory requirement for the thymic microenvironment in the final maturation of the majority of CD4hi SP postselection thymocytes, and demonstrate the existence of a previously unrecognized control point in T cell development.
我们之前已在体外分离并鉴定了CD4高表达T细胞受体（TCR）高表达单阳性（SP）胸腺细胞的两个亚群：CD8阴性和CD8低表达。在本报告中，我们分析了这些“晚期”CD4高表达SP胸腺细胞亚群的表型、功能和发育特征。TCR高表达表型以及对与内源性小鼠乳腺肿瘤病毒（MMTV）产物反应的TCR Vβ片段表达的T细胞的清除表明这两个亚群都经历了阳性和阴性选择。通过以下能力判断，CD8阴性4高表达胸腺细胞具有功能：（a）诱导致死性移植物抗宿主病（GVHD）；（b）在外周淋巴器官中存活并扩增；（c）响应体外TCR交联而增殖而非凋亡。相比之下，CD8低表达4高表达细胞不能诱导GVHD，在外周器官中无法扩增（甚至可能无法存活），并在TCR交联时发生凋亡。然而，当重新引入胸腺时，这些细胞成熟为有功能的、长寿的CD8阴性4高表达淋巴细胞。这些结果证明了胸腺微环境对大多数CD4高表达SP选择后胸腺细胞最终成熟的强制性要求，并证明了T细胞发育中一个先前未被认识的控制点的存在。
