Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro

Sarcoidosis is a systemic disease characterized by the accumulation of acti vated T cells and widespread granuloma formation. In addition, individual g enetic predisposition appears to be important in this disease. Osteopontin, a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in the granulomas of tuberculosis, and is associated with gen etic susceptibility to intracellular infection. The function of osteopontin in these T cell-mediated responses is unknown. We sought to elucidate the role of osteopontin in granulomatous inflammation by characterizing its exp ression in different stages of sarcoidosis and its effector function on T c ells in vitro, Lymphocyte-associated expression of osteopontin in sarcoidos is was demonstrated by immunohistochemistry, and its expression correlated with granuloma maturity. In addition, osteopontin induced T cell chemotaxis , supported T cell adhesion (an effect enhanced by thrombin cleavage of ost eopontin), and costimulated T cell proliferation, These results suggest a n ovel mechanism by which osteopontin and thrombin modulate T cell recruitmen t and activation in granulomatous inflammation.