Denning Timothy L, Kim Gisen, Kronenberg Mitchell
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
J Immunol. 2005 Jun 15;174(12):7487-91. doi: 10.4049/jimmunol.174.12.7487.
Transfer of CD4(+)CD45RB(high) T cells into RAG(-/-) mice causes colitis, which can be prevented by CD4(+)CD25(+) regulatory T cells (Treg). Colitis induction by CD4(+)CD45RB(high) T cells requires beta(7) integrin-dependent intestinal localization, but the importance of beta(7) integrins for Treg function is unknown. In this study, we show that beta(7)(-/-) Treg were effective in preventing colitis. Treg expanded in vivo to the same extent as CD4(+)CD45RB(high) T cells after transfer and they did not inhibit CD4(+)CD45RB(high) T cell expansion in lymphoid tissues, although they prevented the accumulation of Th1 effector cells in the intestine. beta(7)(-/-) Treg were significantly reduced in the large intestine, however, compared with wild-type Treg, and regulatory activity could not be recovered from the intestine of recipients of beta(7)(-/-) Treg. These data demonstrate that Treg can prevent colitis by inhibiting the accumulation of tissue-seeking effector cells and that Treg accumulation in the intestine is dispensable for colitis suppression.
将CD4(+)CD45RB(high) T细胞转移至RAG(-/-)小鼠体内会引发结肠炎，而CD4(+)CD25(+)调节性T细胞（Treg）可预防这种结肠炎。CD4(+)CD45RB(high) T细胞诱导结肠炎需要β(7)整合素依赖性肠道定位，但β(7)整合素对Treg功能的重要性尚不清楚。在本研究中，我们发现β(7)(-/-) Treg在预防结肠炎方面有效。转移后，Treg在体内的扩增程度与CD4(+)CD45RB(high) T细胞相同，并且它们不会抑制淋巴组织中CD4(+)CD45RB(high) T细胞的扩增，尽管它们可防止肠道中Th1效应细胞的积累。然而，与野生型Treg相比，β(7)(-/-) Treg在大肠中的数量显著减少，并且无法从接受β(7)(-/-) Treg的受体肠道中恢复调节活性。这些数据表明，Treg可通过抑制趋化至组织的效应细胞的积累来预防结肠炎，并且Treg在肠道中的积累对于抑制结肠炎并非必需。
