A central role for induced regulatory T cells in tolerance induction in experimental colitis.
In addition to thymus-derived or natural T regulatory (nT(reg)) cells, a second subset of induced T regulatory (iT(reg)) cells arises de novo from conventional CD4(+) T cells in the periphery. The function of iT(reg) cells in tolerance was examined in a CD45RB(high)CD4(+) T cell transfer model of colitis. In situ-generated iT(reg) cells were similar to nT(reg) cells in their capacity to suppress T cell proliferation in vitro and their absence in vivo accelerated bowel disease. Treatment with nT(reg) cells resolved the colitis, but only when iT(reg) cells were also present. Although iT(reg) cells required Foxp3 for suppressive activity and phenotypic stability, their gene expression profile was distinct from the established nT(reg) "genetic signature," indicative of developmental and possibly mechanistic differences. These results identified a functional role for iT(reg) cells in vivo and demonstrated that both iT(reg) and nT(reg) cells can act in concert to maintain tolerance.
Haribhai
Dipica
D
Department of Pediatrics, Section of Rheumatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Lin
Wen
W
Edwards
Brandon
B
Ziegelbauer
Jennifer
J
Salzman
Nita H
NH
Carlson
Marc R
MR
Li
Shun-Hwa
SH
Simpson
Pippa M
PM
Chatila
Talal A
TA
Williams
Calvin B
CB
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins