Lee H M, Rich S
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
J Immunol. 1993 Jul 15;151(2):668-77.
Transforming growth factor-beta (TGF-beta) is a highly conserved multifunctional factor that broadly regulates cell growth and differentiation, and exhibits diverse regulatory roles in the immune system. In contrast to other studies describing TGF-beta as a potent inhibitor of lymphocyte growth, we have shown previously that TGF-beta 1 can also costimulate proliferation of murine splenic T cells activated by immobilized anti-CD3 antibody. In the present studies, we further investigate the subsets of T cells that are responsive to TGF-beta 1 costimulation. T cells were isolated into CD45RBhi/lo or CD4+/8+ populations, and their responses to TGF-beta 1 were examined. Sorted CD45RBhi cells were highly responsive to TGF-beta 1 costimulation, and proliferated to a level similar to that of unsorted T cells in response to TGF-beta 1. TGF-beta 1 also costimulated proliferation in the CD45RBlo population that was distinguished by low response and delayed kinetics. In contrast, sorted CD4+ and CD8+ T cells showed a striking differential response. Anti-CD3-stimulated proliferation of sorted CD8+ or CD4- T cells was substantially enhanced by TGF-beta 1, whereas sorted CD4+ or CD8- T cells were unresponsive. TGF-beta 1 also down-regulated CD45RB and increased CD44 expression on responsive CD8+ and CD45RBhi T cells, thereby leading to a population of T cells enriched in mature phenotype. Generation of anti-CD3-redirected lytic activity by these TGF-beta 1-costimulated CD8+ cells was strongly suppressed. However, these CD8+ T cells exhibited cytotoxic activity after restimulation in the absence of TGF-beta. TGF-beta 1 precultured CD8+ T cells also had heightened IL-2 and IFN-gamma secretion upon restimulation in comparison to cells activated initially without TGF-beta. CD8+ T cells precultured with anti-CD3 and TGF-beta remained responsive to growth enhancement by TGF-beta, although re-exposure to TGF-beta depressed other functions of these cells. Thus, TGF-beta 1 demonstrates important costimulatory roles in both growth and maturation of CD8+ T cells.
转化生长因子-β（TGF-β）是一种高度保守的多功能因子，广泛调节细胞生长和分化，并在免疫系统中发挥多种调节作用。与其他将TGF-β描述为淋巴细胞生长强效抑制剂的研究不同，我们之前已经表明，TGF-β1还可以共刺激由固定化抗CD3抗体激活的小鼠脾T细胞的增殖。在本研究中，我们进一步研究了对TGF-β1共刺激有反应的T细胞亚群。将T细胞分离为CD45RBhi/lo或CD4+/8+群体，并检测它们对TGF-β1的反应。分选的CD45RBhi细胞对TGF-β1共刺激高度敏感，并在对TGF-β1的反应中增殖到与未分选T细胞相似的水平。TGF-β1还在以低反应性和延迟动力学为特征的CD45RBlo群体中共刺激增殖。相比之下，分选的CD4+和CD8+ T细胞表现出明显的差异反应。TGF-β1显著增强了分选的CD8+或CD4- T细胞的抗CD3刺激增殖，而分选的CD4+或CD8- T细胞无反应。TGF-β1还下调了反应性CD8+和CD45RBhi T细胞上的CD45RB并增加了CD44表达，从而导致富含成熟表型的T细胞群体。这些TGF-β1共刺激的CD8+细胞产生的抗CD3重定向裂解活性受到强烈抑制。然而，这些CD8+ T细胞在没有TGF-β的再刺激后表现出细胞毒性活性。与最初未用TGF-β激活的细胞相比，用TGF-β1预培养的CD8+ T细胞在再刺激时也有更高的IL-2和IFN-γ分泌。用抗CD3和TGF-β预培养的CD8+ T细胞对TGF-β的生长增强仍有反应，尽管再次暴露于TGF-β会抑制这些细胞的其他功能。因此，TGF-β1在CD8+ T细胞的生长和成熟中都显示出重要的共刺激作用。
