Gastroenterology

Gastroenterology

Volume 116, Issue 3, March 1999, Pages 557-565
Gastroenterology

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

Presented in part at the 1997 annual meeting of the American Gastroenterological Association in Washington, DC.
https://doi.org/10.1016/S0016-5085(99)70177-0Get rights and content

Abstract

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.

GASTROENTEROLOGY 1999;116:557-565

Section snippets

Patients

Fourteen patients with CD, 5 patients with UC, 2 patients with diverticulitis, and 21 control patients were studied. In the patients with CD, the disease involved the ileum as primary disease in 10 patients and as recurrent disease in the remaining 4 patients. None of the patients with CD was being treated with either corticosteroids or immunosuppressive agents at the time of surgery; however, in 2 patients with CD, corticosteroid treatment had been discontinued approximately 30 days before

Lamina propria lymphocytes from patients with CD and other GI inflammatory states manifest reduced CD2 pathway activation–associated apoptosis

In previous studies, we have shown that LPMCs from control ileal tissue manifest substantially increased apoptosis, both before stimulation (unstimulated apoptosis) and after CD2 pathway activation for 24 hours (CD2-induced apoptosis) compared with control peripheral blood mononuclear cells. These differences in the percentage of apoptotic cells are not the result of the LPMC isolation procedure because peripheral blood mononuclear cells subjected to a similar isolation procedure do not

Discussion

In this study we show that lamina propria T cells extracted from inflamed lamina propria tissue from patients with CD and other GI inflammatory states, such as UC and diverticulitis, display decreased CD2 pathway–induced apoptosis. Such stimulated apoptosis is a Fas-mediated phenomenon in control lamina propria T cells; in this study we show that the decreased apoptosis in lamina propria T cells from inflamed (CD) ileum is in fact caused by decreased intracellular Fas signaling. These findings

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    Address requests for reprints to: Monica Boirivant, M.D., Laboratory of Immunology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Fax: (39) 06-493-87115.

    ☆☆

    Supported by a grant from Istituto Superiore di Sanità for the following research project: Prevenzione dei fattori di rischio della salute materno-infantile.

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