Osteopontin augments CD3-mediated interferon-gamma and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells

Osteopontin is an RGD-containing bone matrix protein with cytokine-like fun ctions that is associated with early stages of Th1-mediated diseases. Altho ugh the function of osteopontin in these responses is unknown, it is expres sed by activated T cells and macrophages and can costimulate T cell prolife ration. Studies have demonstrated that early IL-12 and IFN-gamma expression is required to induce a protective response to many intracellular pathogen s. Herein, we demonstrate that osteopontin stimulation augments the ability of anti-CDS monoclonal antibody to induce CD40 ligand (CD40L) and IFN-gamm a expression on human T cells, resulting in CD40L- and IFN-gamma-dependent IL-12 production in vitro. These findings suggest a functional role for ost eopontin in early Th1 responses, namely regulation of T cell-dependent IL-1 2 production. Further, osteopontin up-regulation of CD40L provides mechanis tic support for the association of osteopontin with polyclonal B cell proli feration and humoral autoimmune disease.