Alimentary TractLamina propria T cells in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis☆,☆☆
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
References (30)
- et al.
Activation induced cell death (apoptosis) of mature peripheral T lymphocytes
Immunol Today
(1993) - et al.
Cellular environments and apoptosis: tissue microenvironment control activated T-cell death
Immunol Today
(1997) - et al.
Activation and signaling status of human lamina propria T lymphocytes
Gastroenterology
(1991) - et al.
Fas-induced activation of the cell death-related protease CPP32 is inhibited by Bcl-2 and by ICE family protease inhibitors
J Biol Chem
(1996) - et al.
Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease
Gastroenterology
(1991) - et al.
Immunobiology and immunopathology of human gut mucosa: humoral immunity and intraepithelial lymphocytes
Gastroenterology
(1989) - et al.
Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis
J Clin Invest
(1996) - et al.
Differential responsiveness to CD3-Ti vs. CD2-dependent activation of human intestinal T lymphocytes
Eur J Immunol
(1990) - et al.
Definition of lamina propria T cell responsive state. Enhanced cytokine responsiveness of T cells stimulated through the CD2 pathway
J Immunol
(1995) - et al.
Hypo-proliferative human lamina propria T cells retain the capacity to secrete lymphokines when stimulated via the CD2/CD28 accessory signaling pathways
Proc Assoc Am Physicians
(1996)
Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease
J Immunol
Spontaneous release of interferon γ by intestinal lamina propria lymphocytes in Crohn's disease: kinetics of in vitro response to interferon γ inducers
Gut
Tumor necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine
Clin Exp Immunol
Interleukin-2 and interferon-gamma secreting T cells in normal and diseased human intestinal mucosa
Immunology
Isolation and functional characterization of human mucosal lymphoid cells
J Clin Invest
Cited by (240)
Can molecular stratification improve the treatment of inflammatory bowel disease?
2019, Pharmacological ResearchSurvivin and autoimmunity; the ins and outs
2018, Immunology LettersP2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells
2017, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCrohn's Disease
2015, Mucosal Immunology: Fourth EditionLymphocyte Trafficking to Mucosal Tissues
2015, Mucosal Immunology: Fourth Edition
- ☆
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.