CD40 expression by gingival fibroblasts: correlation of phenotype with function

CD40, a member of the tumor necrosis factor-alpha receptor family, isconstitutively expressed by cells of hematopoietic and non- hematopoieticorigin, including fibroblasts. Signaling through this receptor moleculeregulates inflammatory cytokine secretion by many cell types. Based on therecently described cytokine secretory heterogeneity of fibroblast cellsubsets, we hypothesized that secretion of inflammatory cytokines bygingival fibroblast cultures may be dictated by the existence ofdifferential proportions of cytokine- secreting subpopulations whichexpress high levels of CD40. After examining a large number of gingivalfibroblast (GF) cultures we find that the frequency of IL-6- andIL-8-secreting cells mirrors the frequency of cells expressing high levelsof CD40 in these cultures. In addition, we demonstrate a direct functionalrelationship between CD40 expression and IL-6 or IL-8 secretion by showingthat ligation of this molecule on GF, and CD40+ fibroblast subsets inparticular, up- regulates secretion of these cytokines in vitro.