Altered expression of alpha 4 beta 7, a gut homing integrin, by circulating and mucosal T cells in colonic mucosal inflammation

Gut. 1997 Feb;40(2):241-6. doi: 10.1136/gut.40.2.241.

Abstract

Background and aims: Expression of alpha 4 beta 7 on memory T lymphocytes identifies a cell population that preferentially migrates to the gut. Detection of alpha 4 beta 7 on circulating lymphocytes may permit the identification of specific subsets trafficking between the circulation and the gut in inflammatory bowel diseases.

Patients: Samples and clinical details were taken from patients with Crohn's disease (CD), ulcerative colitis (UC), diverticulitis/ infectious colitis, and healthy controls.

Methods: Peripheral blood and lamina propria mononuclear cells were isolated. Cells were labelled with CD3, CD4, CD25, CD45RO or alpha 4 beta 7.

Results: Median levels of circulating total memory T cells (CD4+CD45RO+) were increased in CD (p < 0.01) and UC (p < 0.05). However, the proportion of systemic gut homing T cells (CD4+CD45RO+ alpha 4 beta 7+) was decreased in CD (p < 0.05), UC (p < 0.002), and inflammatory controls (p < 0.05). Levels of activated gut homing T cells (CD4+CD25+ alpha 4 beta 7+) were increased in CD (p < 0.01) and UC (p < 0.05). For both CD4+CD45RO+ and CD4+CD25+ cells, the proportion of lymphocytes coexpressing alpha 4 beta 7 was decreased compared with controls. In small and large intestine lamina propria, expression of alpha 4 beta 7+ on CD3+ cells was extensive, although it was decreased in CD (p < 0.03), UC (p < 0.05), and inflammatory controls (p < 0.05).

Conclusions: Circulating and mucosal gut homing lymphocyte populations are changed in patients with colonic inflammation. This may arise due to a dilution effect from recruited naive T cells, or from integrin down regulation. Changes in general CD4+ lymphocyte populations mask more subtle variations in those cells with gut homing potential.

MeSH terms

  • CD3 Complex / analysis
  • CD4 Antigens / analysis
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism
  • Colon / immunology
  • Colon / metabolism
  • Crohn Disease / immunology
  • Crohn Disease / metabolism
  • Humans
  • Immunologic Memory*
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Integrins / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestine, Small / metabolism
  • Leukocyte Common Antigens / analysis
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • CD3 Complex
  • CD4 Antigens
  • Integrins
  • Receptors, Interleukin-2
  • integrin alpha4beta7
  • Leukocyte Common Antigens