Cutting edge: CD4+CD25+ regulatory T cells impaired for intestinal homing can prevent colitis.
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.
Denning
Timothy L
TL
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Kim
Gisen
G
Kronenberg
Mitchell
M
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D039641:Integrin beta Chains / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D039641:Integrin beta Chains; D015375:Receptors, Interleukin-2; C091368:integrin beta7; D007371:Interferon-gamma