Circulating T cells specific for an intestinal bacterial antigen peptide show a distinctive phenotype and potentially proinflammatory gene expression pattern in Crohn’s disease.

Abstract

Abstract Background Crohn’s disease (CD) may be an inappropriate immune reaction to normally well-tolerated intestinal bacterial antigens. Indeed, many CD patients possess abnormally high titers of antibodies specific for intestinal bacterial proteins, such as the outer membrane protein C (OmpC) of E. coli. Methods Using MHC-II tetramer-guided epitope-mapping, we identified a specific peptide of OmpC recognized by peripheral T cells from HLA-DR1501+ individuals. HLA-DR1501 tetramers loaded with this OmpC peptide or a known antigenic peptide from influenza virus (Flu) were then used to compare OmpC versus Flu-specific T cells from HLA-DR1501+ healthy and CD donors via flow cytometry and multiplex qPCR. Results OmpC-specific T cells more frequently expressed the Th17 marker CD161 (49% v 26%; p=1.1e-18) and the gut-homing integrin α4β7 (43% v 10%; p=1.8e-13) than autologous Flu-specific T cells. Conversely, the Th1 marker CXCR3 was more commonly seen on Flu than OmpC-specific T cells (72% v 61%; p = 0.005). No differences in the frequency or immunophenotype of OmpC-specific T cells were found between healthy and CD patients. However in patients with CD, multiplex PCR of sorted OmpC-specific T cells revealed significantly higher expression of the costimulatory molecule CD226 (p=0.03) compared to healthy controls, with a concomitant trend towards decreased expression of the coinhibitory receptor TIGIT (p=0.1) in CD patients. Conclusions OmpC-specific T cells with a gut-tropic, Th17-like phenotype can be found in the peripheral blood, and may have an imbalance in CD226 and TIGIT expression to favor inflammation in CD.