Colitis is associated with thymic destruction attenuating CD4+25+ regulatory T cells in the periphery.
OBJECTIVE
Syngeneic bone marrow transplantation into the adult tgepsilon26 mouse results in severe wasting disease and colitis. On transplantation, the rudimentary thymus of the adult tgepsilon26 mouse repopulates briefly but quickly regresses in temporal association with the onset of colitis. The aim of this study is to test the hypothesis that treatment of colitis restores thymic capability to generate regulatory T cells (CD4+25+ T(R) cells).


METHODS
Colitis was induced by bone marrow transplantation into adult irradiated tgepsilon26 mice. Colitis was prevented by 3 distinct modalities. CD4+25+ T cells were collected from both the thymus and spleen and studied for regulatory function by an in vitro suppression assay.


RESULTS
CD4+25+ T(R) cells do not develop efficiently in the thymus of bone marrow transplanted adult tgepsilon26 mice, which have a developmental arrest affecting thymic epithelium. By contrast, the thymic epithelium of neonatal tgepsilon26 mice supports development of T(R) cells. Consequently, colitis develops only in adult transplanted mice but not in the neonatally transplanted mice. Treatment of colitis prevents destruction of the thymus of adult transplanted tgepsilon26 mice and T(R) cells are produced.


CONCLUSIONS
The negative impact of colitis on T(R) development in the thymus, which was confirmed in a second model of colitis, has profound implications for the pathogenesis and treatment of human inflammatory bowel disease.
Faubion
William A
WA
Division of Immunology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue RE-204, Boston, MA 02215, USA. faubion.william@mayo.edu
De Jong
Ype P
YP
Molina
Ana Abadia
AA
Ji
Hongbin
H
Clarke
Kareem
K
Wang
Baoping
B
Mizoguchi
Emiko
E
Simpson
Stephen J
SJ
Bhan
Atul K
AK
Terhorst
Cox
C
D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D003092:Colitis / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012008:Recurrence; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D018398:Homeodomain Proteins; D015375:Receptors, Interleukin-2; C064658:RAG-1 protein