A central role for induced regulatory T cells in tolerance induction in experimental colitis. J Immunol 2009 Mar 15;182(6):3461-8
Date
03/07/2009Pubmed ID
19265124Pubmed Central ID
PMC2763205DOI
10.4049/jimmunol.0802535Scopus ID
2-s2.0-65449136307 (requires institutional sign-in at Scopus site) 191 CitationsAbstract
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.
Author List
Haribhai D, Lin W, Edwards B, Ziegelbauer J, Salzman NH, Carlson MR, Li SH, Simpson PM, Chatila TA, Williams CBAuthors
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of WisconsinPippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adoptive TransferAnimals
Cell Differentiation
Cell Survival
Cells, Cultured
Colitis
Disease Models, Animal
Forkhead Transcription Factors
Green Fluorescent Proteins
Immune Tolerance
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Promoter Regions, Genetic
T-Lymphocytes, Regulatory