Evidence for a Th2-type response with colitis has been reported in TCR-deficient mice, which develop spontaneous colitis. diseases, mouse T cells, cytokines, hapten-induced colitis The normal mucosal immune system in the gastrointestinal tract maintains a delicate balance between immunity to microbial pathogens and tolerance Rabbit Polyclonal to 14-3-3 theta to food antigens and indigenous microflora. Despite its importance in protecting against disease and maintaining homeostasis, mucosal immunity is only partially comprehended. What is clear is that the mucosal immune system can be divided into inductive sites and effector regions. The former are termed gut-associated lymphoreticular tissues (GALT)1and include Peyer’s patches, whereas the latter is a lamina propria characterized by more diffuse collections of lymphocytes and plasma cells. Active induction of selected immune responses in the GALT has been shown to lead to either upregulation of antipathogenic responses or to actual suppression of systemic immunity to ubiquitous oral antigens. Inflammatory bowel diseases (IBD) represent chronic, relapsing, and tissue-destructive diseases. Although the etiology of IBD remains unknown, there is circumstantial evidence to link IBD to the mucosal immune system’s failure to attenuate immunity to luminal antigens (1,2). A recent study has shown a primary role for T cells in IBD by demonstrating that anti-CD4 monoclonal antibodies are effective in treating the disease (3). Various experimental murine models of IBD also support a central role for T cells in chronic intestinal inflammation (48). CPI 0610 These models were characterized by an imbalance of regulatory cytokines, most notably by an excessive production of IFN-. A central role for IFN- has been reported in murine colitis following transfer of CD45RBhighT cells toscidmice (4,9,10), by adoptive transfer of T celldepleted bone marrow cells from normal mice into T celldeficient CD3-transgenic mice (11), and in IL-10/mice, which spontaneously develop a severe focal inflammation in both the small and large CPI 0610 intestines (12). Another important mouse model has been introduced to study specific T cell subsets in the intestinal inflammation resulting from 2,4,6-trinitrobenzene sulfonic acid (TNBS)- induced colitis, a system first established in rats (13). The colonic administration of TNBS in 50% ethanol has been shown CPI 0610 to induce a chronic colitis (14,15) as a result of covalent binding of TNP residues to autologous host proteins with subsequent stimulation of delayed-type hypersensitivity to the TNP-modified self antigens (16). Previous studies using SJL/J mice have emphasized that Th1-type responses with production of IL-2 and IFN- are associated with this induced CPI 0610 colitis, and treatment with antiIL-12 antibody markedly decreased the severity of TNBS-induced colitis (14,17). Thus, most mouse IBD models are associated with activated T cells producing cytokines characteristic of a Th1 phenotype, a obtaining in agreement with clinical observations of Crohn’s disease (1820). However, as the production of Th1-type cytokines is not as pronounced in ulcerative colitis as in Crohn’s disease (21,22), we hypothesized that a Th2-type response is also operative in the ulcerative colitis type of chronic intestinal inflammation. In this study, we examined the development of TNBS-induced inflammation in cytokine-deficient mice to determine whether the colitis that develops could be associated with a Th2-type cytokine array. Our results provide the first evidence that Th2-type responses are predominant in TNBS colitis in BALB/c mice and that the resultant disease is usually characterized by hypertrophy of colonic patches. Furthermore, we show that mice undergoing Th2-type responses develop a disease that more closely resembles ulcerative colitis than Crohn’s disease. == Materials and Methods == == Mice. == Normal (IFN-+/+), IFN- genedisrupted (IFN-/), and IL-4 genedisrupted (IL-4/) mice, all around the BALB/c background, were purchased from TheJackson Laboratory. Mice were kept in microisolator cages in animal facilities at The University of Alabama at Birmingham Immunobiology Vaccine CPI 0610 Center. Mice were provided sterile food and water ad libitum and were free of microbial pathogens as determined by antibody.