CD4+CD25+ regulatory T cells cure murine colitis: the role of IL-10, TGF-beta, and CTLA4.
CD4+CD25+ regulatory T cells cure murine colitis: the role of IL-10, TGF-beta, and CTLA4.
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发表时间：
2003
影响因子：
4.4
通讯作者：
Haiying Liu;Bin Hu;Damo Xu;F. Liew
中科院分区：
文献类型：
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作者：
Haiying Liu;Bin Hu;Damo Xu;F. Liew
调节性T细胞在调节免疫应答中至关重要，因此在防御感染和控制自身免疫性疾病中发挥重要作用。然而，调节性T细胞在已建立的疾病中的治疗作用尚未完全建立。在这项研究中，我们提供了直接的证据表明，CD 4（+）CD 25（+）调节性T细胞可以治愈一个既定的，严重的，进行性结肠炎。当用幼稚的CD 4（+）CD 25（-）T细胞过继转移并感染原虫寄生虫硕大利什曼原虫时，SCID小鼠发生了严重的结肠炎。通过从同基因供体转移新鲜分离或活化的CD 4（+）CD 25（+）T细胞，可以完全停止疾病发展，症状逆转，并获得健康的结果。调节性T细胞的治疗作用通过用抗IL-10 R、抗CTLA 4或抗TGF-β Ab治疗受体而被完全阻断。然而，在这些治疗下结肠炎的复发并不伴随着Th 1或Th 2应答的重新激活，也不与寄生虫负荷相关。因此，这些结果表明，CD 4（+）CD 25（+）T细胞是治疗性的，并且该效果由IL-10/TGF-β依赖性和非依赖性机制介导。此外，结肠炎可以独立于Th 1和Th 2应答而表现。
Regulatory T cells are critical in regulating the immune response, and therefore play an important role in the defense against infection and control of autoimmune diseases. However, a therapeutic role of regulatory T cells in an established disease has not been fully established. In this study, we provide direct evidence that CD4(+)CD25(+) regulatory T cells can cure an established, severe, and progressive colitis. SCID mice developed severe colitis when adoptively transferred with naive CD4(+)CD25(-) T cells and infected with the protozoan parasite Leishmania major. The disease development can be completely halted and symptoms reversed, with a healthy outcome, by transferring freshly isolated or activated CD4(+)CD25(+) T cells from syngeneic donors. The therapeutic effect of the regulatory T cells was completely blocked by treatment of the recipients with anti-IL-10R, anti-CTLA4, or anti-TGF-beta Ab. However, the resurgence of colitis under these treatments was not accompanied by the reactivation of Th1 or Th2 response nor was it correlated to the parasite load. These results therefore demonstrate that CD4(+)CD25(+) T cells are therapeutic and that the effect is mediated by both IL-10/TGF-beta-dependent and independent mechanisms. Furthermore, colitis can manifest independent of Th1 and Th2 responses.