Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland; and
Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland; and.
J Leukoc Biol. 2016 Sep;100(3):491-8. doi: 10.1189/jlb.1A0415-164R. Epub 2016 Mar 10.
Although mature human FOXP3(+) regulatory T cells are CD127 (IL-7Rα) negative, CD4(+)CD8(+) FOXP3(+) thymocytes express relatively high levels of CD127 and are responsive to IL-7. However, the role of IL-7 in human regulatory T cell development is poorly known. We show that at the CD4(+)CD8(+) stage, FOXP3(+) thymocytes are highly susceptible to apoptosis, and IL-7 selectively rescues them from death, leading to an increased frequency of FOXP3(+) cells. IL-7 also promotes the development of regulatory T cell phenotype by inducing up-regulation of FOXP3(+) and CTLA-4 expression. In contrast, IL-7 does not enhance proliferation of FOXP3(+)thymocytes or induce demethylation of FOXP3(+) regulatory T cell-specific demethylated region. After the CD4(+)CD8(+) stage, the FOXP3(+) thymocytes down-regulate CD127 expression but despite very low levels of CD127, remain responsive to IL-7. These results suggest that IL-7 affects human regulatory T cell development in the thymus by at least 2 distinct mechanisms: suppression of apoptosis and up-regulation of FOXP3(+) expression.
尽管成熟的人 FOXP3(+)调节性 T 细胞是 CD127（IL-7Rα）阴性的，但 CD4(+)CD8(+)FOXP3(+)胸腺细胞表达相对高水平的 CD127 并且对 IL-7 有反应。然而，IL-7 在人类调节性 T 细胞发育中的作用知之甚少。我们表明，在 CD4(+)CD8(+)阶段，FOXP3(+)胸腺细胞极易发生凋亡，而 IL-7 选择性地将它们从死亡中拯救出来，从而增加 FOXP3(+)细胞的频率。IL-7 通过诱导 FOXP3(+)和 CTLA-4 表达的上调，还促进调节性 T 细胞表型的发育。相比之下，IL-7 不会增强 FOXP3(+)胸腺细胞的增殖，也不会诱导 FOXP3(+)调节性 T 细胞特异性去甲基化区的去甲基化。在 CD4(+)CD8(+)阶段之后，FOXP3(+)胸腺细胞下调 CD127 表达，但尽管 CD127 水平非常低，但仍对 IL-7 有反应。这些结果表明，IL-7 通过至少两种不同的机制影响人类胸腺中的调节性 T 细胞发育：抑制凋亡和上调 FOXP3(+)表达。
