Lamina propria T cells in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis

Gastroenterology. 1999 Mar;116(3):557-65. doi: 10.1016/s0016-5085(99)70177-0.


Background & aims: Normal human lamina propria lymphocytes manifest increased unstimulated apoptosis compared with peripheral lymphocytes, which are enhanced after stimulation via the CD2 activation pathway. This activation-induced apoptosis down-regulates cell expansion and cytokine production. In previous studies, it was shown that lamina propria T cells from patients with Crohn's disease and ulcerative colitis manifest abnormal proliferation and cytokine production. It was therefore of interest to determine if such cells also showed abnormal patterns of apoptosis.

Methods: Apoptosis was evaluated by propidium iodide staining of cells followed by flow cytometric analysis. Fas expression and Bcl-2 levels in cells were evaluated by immunofluorescence.

Results: Lamina propria lymphocytes from patients with Crohn's disease and ulcerative colitis as well as from 2 patients with diverticulitis showed defective CD2 pathway-induced apoptosis. Studies of the mechanisms of this defect focusing on cells from patients with Crohn's disease showed that Crohn's disease lamina propria lymphocytes from inflamed tissues express the same amount of cell surface Fas but are less sensitive to Fas-mediated apoptosis than control cells. In addition, lamina propria lymphocytes from inflamed Crohn's disease tissues manifest increased expression of Bcl-2 after CD2 pathway stimulation and elevated Bcl-2 levels in cultures of unstimulated T cells.

Conclusions: T cells isolated from areas of inflammation in Crohn's disease, ulcerative colitis, and other inflammatory states manifest decreased CD2 pathway-induced apoptosis. Studies of cells from inflamed Crohn's disease tissue indicate that this defect is accompanied by elevated Bcl-2 levels. These changes are probably caused by the chronic inflammation and may aggravate the underlying disease processes that are present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology*
  • Apoptosis*
  • CD2 Antigens / immunology*
  • Cells, Cultured
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / pathology
  • Crohn Disease / immunology*
  • Crohn Disease / pathology
  • Cytokines / biosynthesis
  • Diverticulitis / immunology*
  • Diverticulitis / pathology
  • Flow Cytometry
  • Humans
  • Ileitis / immunology
  • Ileitis / pathology
  • Inflammation
  • Lymphocyte Activation
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Reference Values
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • fas Receptor / immunology


  • Antigens, CD
  • CD2 Antigens
  • Cytokines
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor