Crohn's disease and ulcerative colitis, commonly referred to as idiopathic inflammatory bowel disease (IBD), are chronic recurrent inflammatory conditions of the intestinal tract. They are characterized by repetitive bouts of abdominal pain, bloody diarrhea and weight loss. The cause of these conditions is unknown and there is no cure although they are felt to be a result of both genetic predisposition and environmental influences. The intestinal mucosa seems to become either a target or an innocent bystander involved in an aggressive and unrelenting inflammatory process. The recently discovered CD1d molecule, which has been found to be expressed largely in the intestine, appears to play a role in antigen presentation to the intestinal immune system. This includes its ability to present unique antigens from unique pathogens including Mycobacterial species, which in epidemiologic studies have been implicated in the biology of Crohn's disease. The correlation however, is inconsistant, suggesting the involvement of other, possibly host-related factors in the pathogenesis of this form of IBD. Our unifying hypothesis therefore is, that IBD results from the dysfunctional presentation of environmental antigens (such as that found in Mycobacterial paratuberculosis) by the CD1d system to the intestinal immune system.
The specific aims to validate this hypothesis include: 1) Assess the ability of CD1d to activate, in vitro, intraepithelial lymphocytes (IEL's) isolated from IBD and control patients using mixed lymphocyte reaction and cell mediated cytotoxicity assays' and 2) the generation of a transgenic mouse model constitutively over-expressing the CD1d molecule, to be used in subsequent in vivo studies.
| Page, M J; Poritz, L S; Tilberg, A F et al. (2000) Cd1d-restricted cellular lysis by peripheral blood lymphocytes: relevance to the inflammatory bowel diseases. J Surg Res 92:214-21 |
