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(Journal of Leukocyte Biology. 2006;79:917-922.)
© 2006 by Society for Leukocyte Biology

Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn’s disease

Monica Carol1, Natalia Borruel, Maria Antolin, Marta Llopis, Francesc Casellas, Francisco Guarner and Juan-R. Malagelada

Digestive System Research Unit, University Hospital Vall d’Hebron, Autonomous University of Barcelona, Spain

1Correspondence: Digestive System Research Unit, University Hospital Vall d’Hebron, Passeig Vall d’Hebron 129, E-08035 Barcelona, Spain. E-mail: mcarol{at}vhebron.net

ABSTRACT

Apoptosis of active T lymphocytes constitutes a major control mechanism of immune homeostasis and tolerance. In Crohn’s disease, abnormal activation of mucosal T lymphocytes against enteric bacteria is the key event triggering intestinal inflammation. Resistance of lymphocytes to apoptosis has been proposed as the pathogenetic defect. We examined the influence of bacteria-mucosa interactions on apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from 12 patients with Crohn’s disease. Mucosal explants from each specimen were cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN-114 001, or no bacteria. Cytokine release was measured in supernatant, and mononuclear cells were isolated for phenotypic characterization and Bcl-2 family protein expression. Coculture of inflamed tissue with L. casei significantly reduced the release of interleukin (IL)-6 and tumor necrosis factor {alpha} (P<0.05). In addition, coculture with L. casei significantly reduced the number of T cells displaying the IL-2 receptor in the lamina propria. Expression of the antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no significant effect. In conclusion, L. casei reduces the number of activated T lymphocytes in the lamina propria of Crohn’s disease mucosa. A balanced, local microecology may restore immune homeostasis.

Key Words: human • T lymphocytes • inflammatory disorders • intestinal mucosa






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