The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in gammadelta T cells in large intestinal mucosa

Int J Colorectal Dis. 2010 Sep;25(9):1055-62. doi: 10.1007/s00384-010-0975-9. Epub 2010 Jun 23.

Abstract

Backgrounds and aims: Oral tolerance has previously been shown effective in preventing several immune-mediated disorders in animal models. The aims of this study were to investigate the effect of oral colitis-extracted proteins (CEP) on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice and to explore the relative role of the intestinal mucosal gammadelta T cells.

Methods: The effect of five low oral doses of CEP on colitis was evaluated by clinical manifestation and histological lesions. Serum cytokines were measured by enzyme-linked immunosorbent assay. The percentages of the intestinal mucosal gammadelta T cells were evaluated by flow cytometry.

Results: CEP-fed colitis mice showed less severe symptoms and histological injury than bovine serum albumin (BSA)-fed control mice. Tolerized mice developed an increase in TGF-beta1 and no change in IFN-gamma serum levels. Increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in small intestinal mucosal lymphocytes and no quantitative change in large intestinal mucosal lymphocytes were demonstrated in colitis mice compared to untreated mice. The proportions of TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes from CEP-fed colitis mice were significantly higher compared to BSA-fed controls. The disease activity index negatively correlated with the percentages of large intestinal mucosal gammadelta T cells. Furthermore, mucosal repair in repair-period mice was also accompanied by increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes.

Conclusion: Improvement of DSS-induced colitis that resulted from oral administration of colitis-extracted proteins is associated with an increase in gammadelta T cells in large intestinal mucosa.

MeSH terms

  • Administration, Oral
  • Animals
  • Colitis / blood
  • Colitis / drug therapy
  • Colitis / metabolism*
  • Colitis / pathology
  • Disease Models, Animal
  • Immune Tolerance
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / pathology
  • Interferon-gamma / blood
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Intestine, Large / drug effects
  • Intestine, Large / immunology
  • Intestine, Large / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Proteins / administration & dosage
  • Proteins / pharmacology
  • Proteins / therapeutic use*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta1 / blood
  • Wound Healing / drug effects

Substances

  • Protective Agents
  • Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Transforming Growth Factor beta1
  • Interferon-gamma