Regression of Peyer's patches in G alpha i2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis.
BACKGROUND
G protein deficient (G alpha i2-/-) mice spontaneously develop an inflammatory bowel disease (IBD) closely resembling ulcerative colitis. Previous studies have demonstrated that gut T cells are hyperreactive to the endogenous microflora in most IBD models.


OBJECTIVE
The aim of this study was to analyse Peyer's patches (PP), the inductive sites for gut mucosal immune responses.


METHODS
G alpha i2-/- mice, an animal model for IBD, were analysed using immunological methods with regard to phenotype and function.


RESULTS
We found significantly decreased numbers of PP in G alpha i2-/- mice. Even before the onset of colitis, G alpha i2 deficient animals exhibited diminished size of PP, as judged by histology. This involution of PP was associated with strongly increased levels of apoptotic lymphocytes, associated with decreased levels of antiapoptotic intracellular protein Bcl-2. PP T lymphocytes showed highly elevated production of interferon gamma in response to the enteric flora compared with PP T cells from wild-type mice, which produced predominantly interleukin 10.


CONCLUSIONS
Thus even before the onset of colitis, the PP in G alpha i2 deficient mice is a Th1 dominated milieu associated with downregulated levels of Bcl-2, resulting in increased apoptosis of lymphocytes leading to regression of PP. We speculate that this Th1 dominated microenvironment in the inductive site for mucosal immune responses contributes to the development of colitis in G alpha i2 deficient mice.
Ohman
L
L
Department of Clinical Immunology, Göteborg University, Sweden.
Franzén
L
L
Rudolph
U
U
Birnbaumer
L
L
Hörnquist
E Hultgren
EH
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010581:Peyer's Patches / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D019253:Proto-Oncogene Proteins c-bcl-2; D007371:Interferon-gamma; D019204:GTP-Binding Proteins