Martins Gislâine A, Cimmino Luisa, Shapiro-Shelef Miriam, Szabolcs Matthias, Herron Alan, Magnusdottir Erna, Calame Kathryn
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Nat Immunol. 2006 May;7(5):457-65. doi: 10.1038/ni1320. Epub 2006 Mar 26.
The B lymphocyte-induced maturation protein 1 (Blimp-1) transcriptional repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4(+) T cells, Blimp-1-deficient CD4(+) T cells proliferated more and produced excess interleukin 2 and interferon-gamma but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation.
B淋巴细胞诱导成熟蛋白1(Blimp-1)转录抑制因子是B淋巴细胞终末分化所必需的。在此,我们证明了Blimp-1在T细胞谱系中的功能。缺乏Blimp-1的胸腺细胞存活率降低,且缺乏Blimp-1的小鼠外周效应T细胞更多。缺乏Blimp-1的小鼠早在6周龄时就出现了严重的结肠炎,且缺乏Blimp-1的调节性T细胞在阻断结肠炎发展方面存在缺陷。T细胞受体刺激后,Blimp-1 mRNA表达显著增加。与野生型CD4(+) T细胞相比,缺乏Blimp-1的CD4(+) T细胞在T细胞受体刺激后增殖更多,产生过量的白细胞介素2和干扰素-γ,但白细胞介素10减少。这些结果强调了Blimp-1在控制T细胞稳态和激活方面的关键作用。