SEVERE COLITIS IN MICE WITH ABERRANT THYMIC SELECTION

Tg epsilon 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 ad ult Tg epsilon 26 mice. Here, we report that T cell-reconstituted adul t Tg epsilon 26 mice develop a spontaneous wasting syndrome characteri zed by extensive inflammation of the colon, resembling human ulcerativ e colitis. Colitis in these animals was marked by substantial infiltra tion of the colon by activated thymus-derived CD4(+) T cells. Importan tly, bone marrow-transplanted Tg epsilon 26 mice previously engrafted with a fetal Tg epsilon 26 thymus did not develop colitis. These resul ts suggest that T cells selected in an aberrant thymic microenvironmen t contain a population of cells able to induce severe colitis that can be prevented by T cells that have undergone normal thymic development .