CD40 EXPRESSION BY GINGIVAL FIBROBLASTS - CORRELATION OF PHENOTYPE WITH FUNCTION

CD40, a member of the tumor necrosis factor-alpha receptor family, is constitutively expressed by cells of hematopoietic and non-hematopoiet ic origin, including fibroblasts, Signaling through this receptor mole cule regulates inflammatory cytokine secretion by many cell types, Bas ed on the recently described cytokine secretory heterogeneity of fibro blast cell subsets, we hypothesized that secretion of inflammatory cyt okines by gingival fibroblast cultures may be dictated by the existenc e of differential proportions of cytokine-secreting subpopulations whi ch express high levels of CD40. After examining a large number of ging ival fibroblast (GF) cultures we find that the frequency of IL-6- and IL-8-secreting cells mirrors the frequency of cells expressing high le vels of CD40 in these cultures, In addition, we demonstrate a direct f unctional relationship between CD40 expression and IL-6 or IL-8 secret ion by showing that ligation of this molecule on GF, and CD40(+) fibro blast subsets in particular, up-regulates secretion of these cytokines in vitro.