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,§
*
Laboratory of Experimental Immunology,
Department of Gastroenterology, and
Department of Pathology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium; and
§
Tanox Pharma, Amsterdam, the Netherlands
CD40 ligand (CD40L or CD154), a type II membrane protein with
homology to TNF, is transiently expressed on activated T cells and
known to be important for B cell Ig production and for activation and
differentiation of monocytes and dendritic cells. Both Crohn’s disease
and ulcerative colitis are characterized by local production of
cytokines such as TNF and by an influx of activated lymphocytes into
inflamed mucosa. Herein, we investigated whether CD40L signaling
participates in immune responses in these diseases. Our results
demonstrated that CD40L was expressed on freshly isolated lamina
propria T cells from these patients and was functional to induce IL-12
and TNF production by normal monocytes, especially after IFN-
priming. The inclusion of a blocking mAb to CD40L or CD40 in such
cocultures significantly decreased monocyte IL-12 and TNF production.
Moreover, lamina propria and peripheral blood T cells from these
patients, after in vitro activation with anti-CD3, showed increased
and prolonged expression of CD40L as compared with controls.
Immunohistochemical analyses indicated that the number of
CD40+ and CD40L+ cells was significantly
increased in inflamed mucosa, being B cells/macrophages and
CD4+ T cells, respectively. These findings suggest that
CD40L up-regulation is involved in pathogenic cytokine production in
inflammatory bowel disease and that blockade of CD40-CD40L interactions
may have therapeutic effects for these patients.
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