CD45RChighCD4+Intestinal Mucosal Lymphocytes Infiltrating in the Inflamed Colonic Mucosa of a Novel Rat Colitis Model Induced by TNB Immunization

Abstract

To clarify the role of CD4⁺intestinal mucosal lymphocytes in chronic intestinal inflammation, we developed a new rat colitis model by immunization with 2,4,6-trinitrobenzenesulfonic acid (TNB) in an emulsion with an adjuvant followed by transrectal administration of a low dose of TNB. Moreover, we assessed the therapeutic effect of anti-CD4 monoclonal antibody (mAb) on this model. In concert with the development ofserum anti-TNB Abs, transmural and segmental colitis that mimics some characteristics of human Crohn's disease was induced in the immunized rats. Immunohistochemical analysis showed the increase of infiltrating lamina propria CD4⁺T cells. Flow-cytometric analysis of isolated cells from inflamed mucosa revealed that CD45RC^highCD4⁺T cells were significantly increased. Interestingly, intraperitoneal administration of anti-CD4 mAbs could suppress severe inflammation in the model with decrease of anti-TNB Ab titer. After the treatment with anti-CD4 mAbs, CD45RC^highCD4⁺T cells in the lamina propria and interferon-γ mRNA expression in the colonic lamina propria CD4⁺T cells were decreased. These results indicated that Th1 CD4⁺intestinal mucosal T cells have a role in the progress of inflamed lesions in chronic enteritis. They implicate that a therapy targeting mucosal T cells expressing CD4 may be feasible in the treatment of human Crohn's disease.