Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora
Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora
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DOI：
10.4049/jimmunol.169.11.6112
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发表时间：
2002-12-01
影响因子：
4.4
通讯作者：
Elson, CO
中科院分区：
文献类型：
--
作者：
Cong, YZ;Weaver, CT;Elson, CO
我们之前的研究表明，盲肠细菌Ag （CBA）特异性CD4(+) T细胞在转移到SCID小鼠体内时可诱导结肠炎。本研究的目的是在C3H/HeJBir （Bir）小鼠中生成和表征cba特异性调节性T细胞。在IL-10存在的情况下，每10-14天用cba脉冲APC刺激CD4(+) T细胞。在四个或更多周期后，这些T细胞产生高水平的IL-10，低水平的IL-4和ifn - γ，而不产生IL-2，与T调节-1 （Tr1）细胞的表型一致。Bir Tr1细胞增殖较差，但其增殖依赖于CD28-B7的相互作用，并且受MHC ii类限制。将Bir Tr1细胞转移到SCID小鼠中不会导致结肠炎，并且将Bir Tr1 T细胞与致病性Bir CD4(+) Th1细胞共转移可预防结肠炎。Bir Tr1细胞在体外抑制cba特异性Th1细胞株的增殖和ifn - γ的产生。这种抑制部分是由于IL-10和TGFbeta1，但与apc或Th1细胞的同源相互作用也参与其中。正常肠固有层CD4(+) T细胞在cba脉冲APCs刺激下具有tr1样活性。我们得出结论，具有TO细胞特性的CD4(+) T细胞存在于肠固有层中，并假设这些细胞维持肠道对肠道菌群的免疫稳态。
We showed previously that cecal bacterial Ag (CBA)-specific CD4(+) T cells induce colitis when transferred into SCID mice. The purpose of this study was to generate and characterize CBA-specific regulatory T cells in C3H/HeJBir (Bir) mice. CD4(+) T cells were stimulated with CBA-pulsed APC in the presence of IL-10 every 10-14 days. After four or more cycles, these T cells produced high levels of IL-10, low levels of IL-4 and IFN-gamma, and no IL-2, consistent with the phenotype of T regulatory-1 (Tr1) cells. Bir Tr1 cells proliferated poorly, but their proliferation was dependent on CD28-B7 interactions and was MHC class II-restricted. Transfer of Bir Tr1 cells into SCID mice did not result in colitis, and cotransfer of Bir Tr1 T cells with pathogenic Bir CD4(+) Th1 cells prevented colitis. Bir Tr1 cells inhibited proliferation and IFN-gamma production of a CBA-specific Th1 cell line in vitro. Such inhibition was partly due to IL-10 and TGFbeta1, but cognate interactions with either APCs or Th1 cells were also involved. Normal intestinal lamina propria CD4(+) T cells had Tr1-like activity when stimulated with CBA-pulsed APCs. We conclude that CD4(+) T cells with the properties of TO cells are present in the intestinal lamina propria and hypothesize that these cells maintain intestinal immune homeostasis to the enteric flora.