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Osteopontin augments CD3‐mediated interferon‐γ 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 functions that is associated with early stages of Th1‐mediated diseases. Although the function of osteopontin in these responses is unknown, it is expressed by activated T cells and macrophages and can costimulate T cell proliferation. Studies have demonstrated that early IL‐12 and IFN‐γ expression is required to induce a protective response to many intracellular pathogens. Herein, we demonstrate that osteopontin stimulation augments the ability of anti‐CD3 monoclonal antibody to induce CD40 ligand (CD40L) and IFN‐γ expression on human T cells, resulting in CD40L‐ and IFN‐γ‐dependent IL‐12 productionin vitro. These findings suggest a functional role for osteopontin in early Th1 responses, namely regulation of T cell‐dependent IL‐12 production. Further, osteopontin up‐regulation of CD40L provides mechanistic support for the association of osteopontin with polyclonal B cell proliferation and humoral autoimmune disease.