Potent induction of activin A secretion from monocytes and bone marrow stromal fibroblasts by cognate interaction with activated T cells.
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-gamma. 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.
Abe
Masahiro
M
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan. masabe@clin.med.tokushima-u.ac.jp
Shintani
Yasumi
Y
Eto
Yuzuru
Y
Harada
Kazuyo
K
Kosaka
Masaaki
M
Matsumoto
Toshio
T
D028341:Activins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D019556:COS Cells; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism*; D038681:Follistatin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D028322:Inhibin-beta Subunits / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D009000:Monocytes / Q000378:metabolism*; D016853:Muromonab-CD3 / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017252:CD3 Complex; D019013:CD40 Antigens; C497964:CD86 protein, human; D038681:Follistatin; D007375:Interleukin-1; D007376:Interleukin-2; D008222:Lymphokines; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; C422405:activin A; D028341:Activins; D023201:CD40 Ligand; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D028322:Inhibin-beta Subunits