CD40 is expressed on human peritoneal mesothelial cells and upregulates the production of interleukin-15 and RANTES

Limited data are available concerning the interaction between lymphocytes a nd human peritoneal mesothelial cells (HPMC) during peritonitis. CD40 is a member of the tumor necrosis factor (TNF) family of receptors whose ligand (CD154) is mainly expressed on the membrane of activated CD4-positive lymph ocytes. CD154-CD40 cross-linking is a central event in antigen presentation , B-cell activation by T cells, and regulation of cytokine secretion from v arious types of cells. The goal of this study was to demonstrate in virro t he presence of CD40 on HPMC and to test its functionality in inducing inter leukin-15 (IL-15) and RANTES. We assayed the levels of CD40 by reverse tran scription-PCR and flow cytometry and IL-15 and RANTES by enzyme-linked immu nosorbent assay. Genetically modified L cells that express elevated levels of CD 154 (CD40L cells) were used to stimulate CD40. HPMC express CD40 mRNA and protein. After stimulation with interferon-gamma (IFN gamma, 5 U/ml) o r TNF alpha (I ng/ml), there was a small increase in CD40 mRNA and protein levels; when both cytokines were applied, the increase in CD40 levels was m ore than threefold. CD40 ligation induced IL-15 production by HPMC and was additive to IFN gamma stimulation. CD40 ligation was strongly synergistic w ith IFN gamma in induction of RANTES (20-fold as compared with unstimulated HPMC), whereas neither ligation nor IFN gamma alone could induce RANTES. P retreatment of HPMC with TNFa and IFN gamma increased the response to CD40 ligation in magnitudes that correlated with the elevation of CD40 levels in duced by the pretreatment. To conclude, the presence of a functional CD40 o n HPMC whose ligation induced IL-15 and RANTES production was detected. It is possible that this receptor acts as a major mediator of T-cell-regulated immune and inflammatory response during peritonitis.