Aw. O'Regan et al., Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro, J IMMUNOL, 162(2), 1999, pp. 1024-1031
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.