Osteopontin augments CD3-mediated interferon-gamma and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells
Aw. O'Regan et al., Osteopontin augments CD3-mediated interferon-gamma and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells, J LEUK BIOL, 68(4), 2000, pp. 495-502
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.