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 activated T cells and widespread granuloma formation. In addition, individual genetic 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 genetic 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 expression in different stages of sarcoidosis and its effector function on T cells in vitro. Lymphocyte-associated expression of osteopontin in sarcoidosis 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 osteopontin), and costimulated T cell proliferation. These results suggest a novel mechanism by which osteopontin and thrombin modulate T cell recruitment and activation in granulomatous inflammation

Abnormal pulmonary granuloma formation in osteopontin-deficient mice

Osteopontin is a novel cytokine that is expressed in pulmonary granulomatous disease such as sarcoidosis and tuberculosis. It can regulate macrophage and T cell migration, activation, and cytokine expression, yet its role in granuloma formation and evolution is unknown. We induced hypersensitivity pulmonary granulomas by embolizing Schistosoma mansoni eggs to the lungs of osteopontin-deficient (null mutant) mice and osteopontin-sufficient (wild-type control) mice. Granulomas from osteopontin-null animals were smaller at early time points and contained remarkably few macrophages and macrophage-derived epithelioid cells and giant cells. T cell accumulation was unaffected by osteopontin deficiency. These results demonstrate that osteopontin regulates macrophage accumulation during pulmonary granuloma formation, and may explain the impaired ability of osteopontin-deficient hosts to control mycobacterial disease