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

Background & Aims: Normal human lamina propria lymphocytes manifest increas ed unstimulated apoptosis compared with peripheral lymphocytes, which ave e n hanced 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 w ith 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 ev aluated by propidium iodide staining of cells followed by flow cytometric: analysis. Fas expression and Bcl-2 levels in cells were evaluated by immuno fluorescence. Results: Lamina propria lymphocytes from patients with Crohn' s disease and ulcerative colitis as well as from 2 patients with diverticul itis showed defective CD2 pathway-induced apoptosis. Studies of the mechani sms of this defect focusing on cells from patients with Crohn's disease sho wed that Crohn's disease lamina propria lymphocytes from inflamed tissues e xpress the same amount of cell surface Fas but are less sensitive to Fas-me diated apoptosis than control cells. In addition, lamina propria lymphocyte s from inflamed Crohn's disease tissues manifest increased expression of Bc l-2 after CD2 pathway stimulation and elevated Bcl-2 levels in cultures of unstimulated T cells. Conclusions: T cells isolated from areas of inflammat ion in Crohn's disease, ulcerative colitis, and other inflammatory states m anifest decreased CD2 pathway-induced apoptosis. Studies of cells from infl amed Crohn's disease tissue indicate that this defect is accompanied by ele vated Bcl-2 levels. These changes are probably caused by the chronic inflam mation and may aggravate the underlying disease processes that are present.