CD40 IS A FUNCTIONAL ACTIVATION ANTIGEN AND B7-INDEPENDENT T-CELL COSTIMULATORY MOLECULE ON NORMAL HUMAN LUNG FIBROBLASTS

CD40 is an important signaling and activation Ag found on certain bone marrow-derived cells, Recently, CD40 also has been shown to be expres sed by mesenchymal cells, including human fibroblasts, Little is known about the role of CD40 in fibroblasts, The current study investigates the hypothesis that CD40 expressed on lung fibroblasts is an activati on structure and mechanism for interaction with hemopoietic cells, Com munication between resident tissue fibroblasts and T cells is necessar y for normal wound healing, and can be pathologic, resulting in tissue fibrosis, Signaling through CD40 with soluble CD40 ligand stimulated fibroblast activation, as evidenced by mobilization of nuclear factor- kappa B and by induction of the proinflammatory and chemoattractant cy tokines IL-6 and IL-8, IFN-gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing CD40, but not the well-studied cos timulatory molecules B7-1 and B7-2, Data reported herein support the h ypothesis that cognate interactions between tissue fibroblasts and inf iltrating T lymphocytes, via the CD40/CD40L pathway, augment inflammat ion and may promote fibrogenesis by activating both cell types.