Severe colitis in mice with aberrant thymic selection

Georg A. Holländer, Stephen J. Simpson, Emiko Mizoguchi, Aliki Nichogiannopoulou, Jian She, José Carlos Gutierrez-Ramos, Atul K. Shan, Steven J. Burakoff, Baoping Wang, Cox Terhorst

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

Tgε{lunate}26 mice display an arrest very early in T cell development that has a profound effect on the architecture of thymic stromal cells. We have recently demonstrated that transplantation of wild-type bone marrow cells restores the thymic microenvironment of fetal but not adult Tgε{lunate}26 mice. Here, we report that T cell-reconstituted adult Tgε{lunate}26 mice develop a spontaneous wasting syndrome characterized by extensive Inflammation of the colon, resembling human ulcerative colitis. Colitis in these animals was marked by substantial Infiltration of the colon by activated thymus-derived CD4+ T cells. Importantly, bone marrow-transplanted Tgε{lunate}26 mice previously engrafted with a fetal Tgε{lunate}26 thymus did not develop colitis. These results suggest that T cells selected In an aberrant thymic microenviron-ment contain a population of cells able to Induce severe colitis that can be prevented by T cells that have undergone normal thymic development.

Original languageEnglish
Pages (from-to)27-38
Number of pages12
JournalImmunity
Volume3
Issue number1
DOIs
StatePublished - Jul 1995
Externally publishedYes

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