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

Scand J Gastroenterol. 2013 Nov;48(11):1278-85. doi: 10.3109/00365521.2013.837952.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / physiology*
  • Clone Cells
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology*
  • Colonoscopy
  • Crohn Disease / immunology
  • Crohn Disease / microbiology
  • Crohn Disease / pathology*
  • Escherichia coli / physiology*
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Mycobacterium avium subsp. paratuberculosis / physiology*

Substances

  • Interleukin-17
  • Interleukin-10
  • Interferon-gamma