Chang J F, Thomas C A, Kung J T
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284.
J Immunol. 1991 Aug 1;147(3):860-6.
Th cell development inside the thymus can be defined on the basis of qualitative and quantitative CD4 and CD8 marker expression and follows the pathway of CD4-8- cells----CD4+8+ cells----CD4+8low cells----CD4+8- cells, which presumably emigrate to seed the periphery and serve as functionally mature Th cells. The various cell subpopulations at defined developmental stages were isolated by electronic cell sorting and examined for mitogen induced IL-2 production and cell proliferation responses. For TCR-alpha beta-bearing CD4+8+ and CD4+8low thymocytes that are actively engaged in positive and negative selection processes, negligible to low levels of IL-2 production and cell proliferation were observed in response to TCR:CD3 triggering or to the combined activation of protein kinase C and calcium mobilization mediated by PMA and ionomycin, respectively. For CD4-8- TCR-alpha beta early thymocytes that have not yet entered the selection process, PMA + ionomycin induced significant cell proliferation but little IL-2 production, in the absence of added IL-1. However, addition of IL-1 caused a powerful induction of IL-2 production that was accompanied by increased cell proliferation. Triggering of the TCR:CD3 complex had no effect on CD4-8-TCR(-)-alpha beta thymocytes as they do not express detectable levels of TCR-alpha beta. For thymus CD4+8- Th cells, the first cells that have completed TCR repertoire selection, vigorous proliferation was observed in response to TCR:CD3 triggering in the presence of added IL-2. However, the development of IL-2 responsiveness was not accompanied by high level IL-2 inducibility as TCR:CD3 triggering caused only marginal IL-2 production. In contrast, spleen CD4+8- T cells, the most "mature" representatives of Th cells, expressed high levels of IL-2 production as well as IL-2 responsiveness in response to TCR:CD3-mediated stimulation. The lack of anti-TCR-induced IL-2 production by thymus CD4+8- T cells was not due to an intrinsic defect as high levels of IL-2 production was induced by PMA + ionomycin. Possible reasons for the temporal acquisition and differential control of IL-2 inducibility and IL-2 responsiveness are discussed in the context of established Th cell development pathway.
胸腺内的辅助性T细胞（Th细胞）发育可根据CD4和CD8标志物的定性和定量表达来定义，并遵循CD4-8-细胞→CD4+8+细胞→CD4+8low细胞→CD4+8-细胞的途径，这些细胞可能迁移至外周并作为功能成熟的Th细胞发挥作用。通过电子细胞分选分离出特定发育阶段的各种细胞亚群，并检测其对丝裂原诱导的白细胞介素-2（IL-2）产生和细胞增殖反应。对于积极参与阳性和阴性选择过程的携带T细胞受体αβ（TCR-αβ）的CD4+8+和CD4+8low胸腺细胞，分别用TCR:CD3触发或用佛波酯（PMA）和离子霉素介导的蛋白激酶C激活和钙动员联合刺激后，观察到IL-2产生和细胞增殖水平可忽略不计或很低。对于尚未进入选择过程的CD4-8-TCR-αβ早期胸腺细胞，在未添加白细胞介素-1（IL-1）的情况下，PMA + 离子霉素诱导显著的细胞增殖，但IL-2产生很少。然而，添加IL-1会强烈诱导IL-2产生，并伴有细胞增殖增加。TCR:CD3复合物的触发对CD4-8-TCR(-)-αβ胸腺细胞没有影响，因为它们不表达可检测水平的TCR-αβ。对于胸腺CD4+8- Th细胞，即第一批完成TCR库选择的细胞，在添加IL-2的情况下，对TCR:CD3触发观察到强烈的增殖反应。然而，IL-2反应性的发展并不伴随着高水平的IL-2诱导性，因为TCR:CD3触发仅引起少量的IL-2产生。相比之下，脾脏CD4+8- T细胞，即Th细胞最“成熟”的代表，在对TCR:CD3介导的刺激反应中表达高水平的IL-2产生以及IL-2反应性。胸腺CD4+8- T细胞缺乏抗TCR诱导的IL-2产生并非由于内在缺陷，因为PMA + 离子霉素可诱导高水平的IL-2产生。在既定的Th细胞发育途径背景下，讨论了IL-2诱导性和IL-2反应性的时间性获得和差异控制的可能原因。
