An increased number of CD40-high monocytes in patients with Crohn's disease

OBJECTIVE: CD40-CD40 ligand (CDL40L) interaction is essential for the T-lym phocyte-dependent immune response. This interaction may be operational in t he pathogenesis of inflammatory bowel diseases (IBD). The present study exa mined the expression of CD40 in peripheral blood mononuclear cells (PBMNCs) and tissue specimens, and CD40-stimulated interleukin (IL)-12 release from PBMNCs in IBD. METHODS: The expression of CD40 in PBMNCs End tissue inflammatory cells was examined by flowcytometry and immunohistochemistry, respectively. IL-12 re lease was measured in cultured media of PBMNCs by an enzyme-linked immunoso rbent assay. RESULTS: Most peripheral blood B-lymphocytes expressed CD40 in all subjects . However, in ulcerative colitis (UC) patients, a significantly increased m ean fluorescence intensity (MFI) of CD40 on B-lymphocytes was detected, com pared with control subjects and patients with Crohn's disease (CD). In cont rast, both the percentage positivity and MFI of CD40 on monocytes of active CD subjects were significantly increased, compared with the other groups. In active CD patients, a high level of IL-12 release from PBMNCs was observ ed by CD40 stimulation, compared with those of the other groups. When prime d with IFN-gamma, PBMNCs from inactive CD patients released a significantly high level of IL-12, probably via stimulation by the CD40 monoclonal antib ody. In the affected mucosa of CD, numerous CD40-positive cells were demons trated, and they were also CD68-positive, suggesting these double CD40/CD68 -positive cells are tissue macrophages. CONCLUSIONS: These results suggest that the examination of CD40 expression in PBMNCs might enable the differentiation of CD from UC. CD40-high monocyt es in CD patients may play a role in the pathogenesis of CD. (Am J Gastroen terol 2000;95:1516-1523. (C) 2000 by Am. Coll. of Gastroenterology).