Immunological abnormality in C3H/HeJ mice with heritable inflammatory bowel disease.
To explore the immunological abnormality of a heritable inflammatory bowel disease developed in a new substrain of C3H/HeJ mice, we examined the expression of integrins beta7 and other cell adhesion molecules on normal and disease mice lymphocytes by flow cytometry. We also examined the cytotoxicity of small intestinal intraepithelial lymphocytes to epithelial cells and the proliferation and aggregation of intestinal lymphocytes. There are several significant changes in the expression levels of alpha4 and alphaM290beta7 integrins, CD11a, ICAM-1, CD45RB, CD4, CD44, and CD45 in different lymphocyte populations. The cytotoxicity of small intestinal intraepithelial lymphocytes from disease mice was higher than that from normal mice and could be stimulated by PHA and inhibited by mAb to alphaM290beta7. The proliferation of both normal and disease small intestinal intraepithelial lymphocytes was enhanced by costimulation by mAb to CD2 or CD3 and ProNectin. In comparison to disease mice, normal small intestinal intraepithelial lymphocytes proliferated at a significantly higher rate in response to sheep RBC and mAb to CD2 or CD3 and ProNectin costimulation. Homotypic aggregation of small intestinal intraepithelial lymphocytes isolated from disease mice was greater than in those from normal mice. The abnormality of expression of integrin beta7 and other cell adhesion molecules and cytotoxic, proliferative, and aggregative responses of lymphocytes from disease mice may play important roles in the pathogenesis of this heritable inflammatory bowel disease.
Ni
J
J
Department of Medicine, University of California, Irvine, 92717, USA.
Chen
S F
SF
Hollander
D
D
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology; D016023:Integrins / Q000032:analysis*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H
D015703:Antigens, CD; D016023:Integrins