and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells
The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts
Correspondence: Jeffrey S. Berman, M.D., Professor of Medicine, The Pulmonary Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. E-mail: jberman{at}lung.bumc.org
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-
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- expression on human
T cells, resulting in CD40L- and IFN--dependent IL-12 production
in 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.
Key Words: human • T lymphocytes • Th1 cytokines • costimulatory molecules • inflammation
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