Expression of CD40 and its ligand, CD40L, in intestinal lesions of Crohn'sdisease

OBJECTIVE: Selected mechanisms of the immune system participate in the deve lopment of inflammatory bowel disease. Recently, overexpression of the liga nd for CD40 (CD40L), a lymphocyte costimulatory molecule, was shown to indu ce severe inflammatory bowel disease in transgenic mice. In the present stu dy, we examined the expression of CD40 and CD40L on surgical specimens of i leum from 12 patients with Crohn's disease and 10 patients with diverticuli tis. METHODS: Several CD40L(+) cells were present in the affected tissue of pati ents with Crohn's disease, whereas few scattered CD40L+ cells were detected in sections of histologically normal ileum, resected distantly from the af fected tissue, in patients with diverticulitis and in normal ileum portions obtained from colorectal cancer undergoing extensive surgery. The phenotyp e of CD40L(+) cells was mainly CD4(+). RESULTS: In patients with Crohn's disease, several CD40(+) cells were detec table in the same areas of lymphocytes expressing CD40L, whereas in patient s with diverticulitis, the number of CD40+ cells was significantly lower. M ost of the CD40+ cells costained with CD20, thus showing to be B-lymphocyte s, and only a few were CD14(+) macrophages. Several von Willebrand-positive vessels were also positive for CD40. In addition, several infiltrating mac rophages were found to express B7-1 and B7-2 molecules, the ligands of CD28 and CTLA-4, which cooperate with the CD40-CD40L pathway in lymphocyte acti vation. Staining of ileaI lesions with anti-CTLA-4 antibodies resulted in d etection of none or very few positive cells. In contrast, in patients with diverticulitis, an enhanced number of B7-1 and B7-2 and CTLA-4 was observed . CONCLUSION: The local accumulation of CD40L(+) together with CD40+ cells wi thin intestinal lesions of Crohn's disease suggests the involvement of this co-stimulatory pathway. (C) 1999 by Am. Cell. of Gastroenterology.