First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan; and
Ajinomoto Central Research Institute, Kanagawa, Japan
Correspondence: Masahiro Abe, First Department of Internal Medicine, School of Medicine, University of Tokushima, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. E-mail: masabe{at}clin.med.tokushima-u.ac.jp
Activin A is a multifunctional cytokine essential for cell differentiation and apoptosis including erythroid cell differentiation in the bone marrow. In addition, activin A is induced by inflammation and exerts anti-inflammatory effects. However, the mechanism of activin A induction is still unclear, especially by inflammatory processes. Here we show that activin A secretion from monocytes and bone marrow stromal fibroblasts, its major sources in the bone marrow, is markedly enhanced by cognate interaction with activated T cells. This process is mediated by CD40/CD40 ligand interaction as well as concomitantly secreted T cell-derived cytokines, granulocyte macrophage-colony stimulating factor, and interferon-
. Furthermore, stromal fibroblasts as well as monocytes provide a costimulatory signal to anti-CD3-treated T cells via CD80 and CD86 to maintain the enhanced activin A production. These findings suggest that activin A is potently induced in the bone marrow and may play a role in the suppression of inflammatory or immune processes.
Key Words: CD40 • CD28 • costimulation • GM-CSF • IFN-
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