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The Journal of Immunology, 2005, 174: 7487-7491.
Copyright © 2005 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: CD4+CD25+ Regulatory T Cells Impaired for Intestinal Homing Can Prevent Colitis1,2

Timothy L. Denning3, Gisen Kim3 and Mitchell Kronenberg4

Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121

Transfer of CD4+CD45RBhigh T cells into RAG–/– mice causes colitis, which can be prevented by CD4+CD25+ regulatory T cells (Treg). Colitis induction by CD4+CD45RBhigh T cells requires {beta}7 integrin-dependant 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+CD45RBhigh T cells after transfer and they did not inhibit CD4+CD45RBhigh 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.




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