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 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.
Holländer
G A
GA
Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Simpson
S J
SJ
Mizoguchi
E
E
Nichogiannopoulou
A
A
She
J
J
Gutierrez-Ramos
J C
JC
Bhan
A K
AK
Burakoff
S J
SJ
Wang
B
B
Terhorst
C
C
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D003093:Colitis, Ulcerative / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D016130:Immunophenotyping; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology
D016827:CD8 Antigens