Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20394-8. doi: 10.1073/pnas.0909954106. Epub 2009 Nov 17.
T cells transferred into severe lymphopenic hosts undergo rapid proliferation known as "endogenous proliferation" that are distinct from conventional homeostatic proliferation. Unlike homeostatic proliferation, cytokines, such as IL-7 are dispensable, yet TCR:MHC interaction is essential for this process to occur. However, cell types inducing the proliferation have not formally been addressed. In this study, we report that CD11c+ conventional DCs play irreplaceable roles in inducing endogenous proliferation of both naive and memory phenotype CD4 T cells via TCR-MHC II interaction. By contrast, CD8 T-cell endogenous proliferation was independent of MHC I or CD11c+ DCs. Interestingly, MHC II was necessary to support naive CD8 T-cell proliferation within MHC I-deficient hosts. Depletion of both B cells and DCs was sufficient to abrogate the proliferation of naive but not of memory CD8 T cells. These results suggest that depending on the T-cell lineages, as well as the differentiation status, different mechanisms control endogenous proliferation, revealing in vivo complexity of T-cell proliferation under lymphopenic conditions.
T 细胞转移到严重淋巴缺乏的宿主中会经历快速增殖，称为“内源性增殖”，与传统的稳态增殖不同。与稳态增殖不同的是，细胞因子，如 IL-7，是可有可无的，而 TCR：MHC 相互作用对于这一过程的发生是必不可少的。然而，诱导增殖的细胞类型尚未得到正式解决。在这项研究中，我们报告说，CD11c+ 常规 DC 通过 TCR-MHC II 相互作用在诱导幼稚和记忆表型 CD4 T 细胞的内源性增殖中发挥不可替代的作用。相比之下，CD8 T 细胞的内源性增殖不依赖于 MHC I 或 CD11c+DC。有趣的是，MHC II 对于支持 MHC I 缺陷宿主中幼稚 CD8 T 细胞的增殖是必要的。耗尽 B 细胞和 DC 足以消除幼稚但不记忆 CD8 T 细胞的增殖。这些结果表明，取决于 T 细胞谱系以及分化状态，不同的机制控制内源性增殖，揭示了淋巴缺乏条件下 T 细胞增殖的体内复杂性。
