A Central Role for Induced Regulatory T Cells in Tolerance Induction in Experimental Colitis

被引：183

作者：

Haribhai, Dipica

Lin, Wen ^{[4
]}

Edwards, Brandon

Ziegelbauer, Jennifer

Salzman, Nita H. ^{[2
]}

Carlson, Marc R. ^{[5
]}

Li, Shun-Hwa ^{[3
]}

Simpson, Pippa M. ^{[3
]}

Chatila, Talal A. ^{[4
]}

Williams, Calvin B. ^{[1
]}

机构：

[1] Med Coll Wisconsin, Dept Pediat, Div Rheumatol, Rheumatol Sect, Milwaukee, WI 53226 USA

[2] Med Coll Wisconsin, Dept Pediat, Gastroenterol Sect, Milwaukee, WI 53226 USA

[3] Med Coll Wisconsin, Dept Pediat, Sect Quantitat Hlth Sci, Milwaukee, WI 53226 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Rheumatol Allergy & Immunol, Los Angeles, CA 90095 USA

[5] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 182卷 / 06期

基金：

美国国家卫生研究院;

关键词：

TGF-BETA; CUTTING EDGE; INDEPENDENT REGULATION; FOXP3; EXPRESSION; REG-CELLS; SELF; HELIOS; IKAROS; MICE; DIFFERENTIATION;

D O I：

10.4049/jimmunol.0802535

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. The Journal of Immunology, 2009, 182: 3461-3468.

引用

页码：3461 / 3468

页数：8

共 47 条

[1] CD25+ CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10 [J].