Holländer G A, Simpson S J, Mizoguchi E, Nichogiannopoulou A, She J, Gutierrez-Ramos J C, Bhan A K, Burakoff S J, Wang B, Terhorst C
Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Immunity. 1995 Jul;3(1):27-38. doi: 10.1016/1074-7613(95)90156-6.
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 adult Tg epsilon 26 mice. Here, we report that T cell-reconstituted adult Tg epsilon 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 Tg epsilon 26 mice previously engrafted with a fetal Tg epsilon 26 thymus did not develop colitis. These results suggest that T cells selected in an aberrant thymic microenvironment contain a population of cells able to induce severe colitis that can be prevented by T cells that have undergone normal thymic development.
