Increased frequency of intestinal CD4+ T cells reactive with mycobacteria in patients with Crohn's disease

OBJECTIVE The aim of this study was to assess the frequency of mycobacteria and Escherichia coli reactive T cells in intestinal biopsies from patients with Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS The biopsies were obtained by colonoscopy from adult patients with active CD (n = 5) and active UC (n = 4). The number of CD4+ T cell clones expanded and screened from each patient varied from 383 to 3972 giving a total of 16639 individual clones. The T cell clones were tested for responses to Mycobacterium avium subspecies paratuberculosis (MAP) and E. coli. The cytokine profile of 42 individual T cell clones from four CD patients was assessed. RESULTS The frequency of mycobacteria reactive T cell clones in CD patients ranged from 0.17 to 1.63% and was higher (p = 0.038) than the frequency of E. coli reactive T cells ranging from 0 to 0.18%. No or very low numbers of mycobacteria reactive clones were detected in three UC patients while the fourth UC patient had a frequency similar to what was observed in CD patients. The frequencies of E. coli reactive T cell clones in UC patients ranged from 0 to 0.52%. T cell clones (n = 42) from CD patients all produced IL-17 and/or IFN-γ. Several clones were also able to produce IL-10. CONCLUSIONS The high frequency of intestinal tissue resident T cells reactive to mycobacteria suggests that an adaptive immune response have taken place and argues that these bacteria may contribute to the chronic inflammation in CD.