A role for TGF-β in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood
A role for TGF-β in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood
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DOI：
10.4049/jimmunol.166.12.7282
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发表时间：
2001-06-15
影响因子：
4.4
通讯作者：
Horwitz, DA
中科院分区：
文献类型：
--
作者：
Yamagiwa, S;Gray, JD;Horwitz, DA
在跨越组织相容性障碍的器官移植中，一个难以实现的目标是诱导特异性耐受以避免移植物排斥。大量的证据表明，胸腺产生调节性T细胞，抑制其他T细胞对抗原刺激的反应。我们报道了TGF-β可以诱导人外周血中初始（CD 45 RA（+）RO（-））部分中的某些CD 4（+）T细胞产生强大的接触依赖性抑制活性，该活性不被抗TGF-β或抗IL-10 mAb拮抗。TGF-β对初始CD 4（+）T细胞的共刺激作用上调了CD 25和CTLA-4的表达，增加了它们向活化表型的转化，但减少了活化诱导的凋亡。抑制活性集中在CD 25（+）组分中。这些CD 4（+）CD 25（+）调节细胞阻止CD 8（+）T细胞对同种异体抗原的反应增殖，并阻止其成为细胞毒性效应细胞。此外，这些调节细胞以非常低的数量发挥其抑制活性，并且即使在它们扩增后也保持这些效果。一旦激活，它们的抑制特性是Ag非特异性的。虽然
An elusive goal in transplanting organs across histocompatibility barriers has been the induction of specific tolerance to avoid graft rejection. A considerable body of evidence exists that the thymus produces regulatory T cells that suppress the response of other T cells to antigenic stimulation. We report that TGF-beta can induce certain CD4(+) T cells in the naive (CD45RA(+)RO(-)) fraction in human peripheral blood to develop powerful, contact-dependent suppressive activity that is not antagonized by anti-TGF-beta or anti-IL-10 mAbs. The costimulatory effects of TGF-beta on naive CD4(+) T cells up-regulated CD25 and CTLA-4 expression, increased their transition to the activated phenotype, but decreased activation-induced apoptosis. Suppressive activity was concentrated in the CD25(+) fraction. These CD4(+)CD25(+) regulatory cells prevented CD8(+) T cells from proliferating in response to alloantigens and from becoming cytotoxic effector cells. Moreover, these regulatory cells exerted their suppressive activities in remarkably low numbers and maintained these effects even after they are expanded. Once activated, their suppressive properties were Ag nonspecific. Although