beta7 Integrin expression is not required for the localization of T cells to the intestine and colitis pathogenesis

Clin Exp Immunol. 2002 Jul;129(1):35-42. doi: 10.1046/j.1365-2249.2002.01892.x.

Abstract

beta7 Integrins have been shown to have an important role in the localization of T cells to the intestine. Utilizing two different experimental mouse models of inflammatory bowel disease (IBD), this study was undertaken to determine if beta7 integrin expression is critical for T cell localization to the intestine and colitis pathogenesis. Transfer of CD4+ CD45RBhigh cells into immunodeficient mice results in colitis. To examine the role of beta7 integrins, donor cells were obtained from beta7 integrin gene-deficient animals and disease induction was examined following transfer into severe combined immunodeficiency (SCID) mice. Additionally, beta7 integrin gene-deficient animals were crossed to IL-2-deficient mice and the onset of spontaneous colitis that normally occurs in IL-2-deficient animals was examined. No differences in the onset or severity of spontaneous colitis was noted in animals that were deficient in both beta7 integrin and IL-2. In contrast, the onset of colitis in recipients of T cells from beta7 integrin-deficient donors was delayed significantly. In mice receiving beta7 integrin negative cells, the initial lack of colitis appeared to correlate with fewer numbers of CD3+beta7 integrin -/- donor lymphocytes present in the host colon. The eventual development of disease, however, was associated with increased numbers of donor beta7 integrin -/- lymphocytes. These results show that beta7 integrin expression is not absolutely required for T cell localization to the intestine and colitis pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Chemotaxis, Leukocyte / physiology*
  • Colitis / genetics
  • Colitis / immunology*
  • Crosses, Genetic
  • Disease Models, Animal
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / physiopathology
  • Integrin beta Chains*
  • Integrins / deficiency
  • Integrins / genetics
  • Integrins / physiology*
  • Interleukin-2 / deficiency
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology
  • Leukocyte Common Antigens / analysis
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Receptors, Lymphocyte Homing / deficiency
  • Receptors, Lymphocyte Homing / genetics
  • Receptors, Lymphocyte Homing / physiology*
  • T-Lymphocyte Subsets / pathology*
  • T-Lymphocyte Subsets / transplantation

Substances

  • Integrin beta Chains
  • Integrins
  • Interleukin-2
  • Receptors, Lymphocyte Homing
  • integrin beta7
  • Leukocyte Common Antigens