Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease.

Abstract

The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occurring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn's disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn's and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment.

• Authors: L Mayer, D Eisenhardt
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 86 Issue 4 Pg. 1255-60 (Oct 1990) ISSN: 0021-9738 [Print] United States
• PMID: 2145321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Differentiation, T-Lymphocyte
• CD4 Antigens
• CD8 Antigens

Topics

• Antigens, Differentiation, T-Lymphocyte (analysis)
• CD4 Antigens (analysis)
• CD8 Antigens
• Epithelium (immunology)
• Humans
• Inflammatory Bowel Diseases (etiology, immunology)
• Intestines (immunology)
• Lymphocyte Activation
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Regulatory (immunology)