9th Annual BMRP Investigator Meeting - Abstract
Searching for the Secret of the T cells in Crohn’s Disease
Ingrid Olsen1,2,a, Stig Tollefsen2, Claus Aagaard3, Peter Andersen3, Knut E.A. Lundin4,1 and Ludvig M. Sollid1
1Centre for Immune Regulation, Institute of Immunology, Oslo University Hospital (Oslo, Norway); 2National Veterinary Institute (Oslo, Norway); 3Department of Infectious Disease Immunology, Statens Serum Institut (Copenhagen, Denmark); 4Department of Medicine, Oslo University Hospital (Oslo, Norway)
The intestinal lesions in Crohn’s disease (CD) consist of lymphoid aggregates with abundance of CD4+ T cells that produce inflammatory cytokines like IL-17 and IFN-γ. T cells have both memory and specificity, which are two features that make them extremely interesting for investigations into the relative importance of various bacteria in the ability to elicit an inflammatory T cell response in CD patients. Studies of the specificity of intestinal T-cells in CD are, however, surprisingly scarce. Duchman et al. (SJI 1996, Gut 1999) showed that both CD and ulcerative colitis (UC) patients had T cells with reactivity to various commensal bacteria, including E. coli, however no differences were found between the two groups. We have previously shown that Mycobacterium avium subsp. paratuberculosis (MAP) reactive T-cell clones that produced IFN-γ and/or IL-17 were present in the intestine of patients with CD (PloS One 2009). These studies are now extended into looking at the frequency of MAP reactive and E. coli reactive T cells by direct cloning, expansion and testing of single CD4+ T cells from intestinal biopsies. Furthermore we are aiming to identify the peptide specificities of the MAP reactive T cell clones using various strategies. To date we have identified three T-cell clones that react to a protein called esxH. This protein belongs to the same family as the identified target of an intestinal T-cell clone described in our previous study.Further work on the newly isolated clones includes identification of HLA restriction, mapping of the exact epitope and testing for cross-reactivity to other mycobacteria.
a Principal Investigator