TGF-beta 1 pretreatment impairs the allostimulatory function of human bone marrow-derived antigen-presenting cells for both naive and primed T cells.
Transforming growth factor-beta (TGF-beta) exhibits strong antiproliferative effects upon lymphocytes and inhibits many of the effector functions of activated immune cells. However, its influence on the inductive phase of immune responses, and in particular its effect on antigen-presenting cells (APC), has not been well studied. In this investigation, we examined the influence of human TGF-beta 1 on the antigen-presenting function of human bone marrow (BM)-derived APC propagated in liquid culture for 11-17 days in response to granulocyte/macrophage colony-stimulating factor (GM-CSF). These cells were predominantly macrophages, accompanied by a minor population of dendritic cells. TGF-beta 1 had no effect upon the allostimulatory function of vertebral body whole BM cells cultured for 3-5 days in GM-CSF. However, it markedly reduced the allostimulatory capacity of BM-derived APC exposed to the cytokine for the last 3 days of culture. This inhibitory action could not be ascribed to cytokine 'carry-over', or to any consistent changes in the expression of cell surface molecules implicated in antigen presentation (HLA-DR), intercellular adhesion (ICAM-1; CD54), or costimulatory activity (B7-1; CD80). Mechanisms that may underlie the inhibitory action of TGF-beta on APC function and the immunologic and possible clinical implications of the findings are discussed.
Pittsburgh Transplantation Institute, University of Pittsburgh, Pennsylvania 15213-2582, USA.
C A
CA
Bonham
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Lu
R A
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Banas
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Fontes
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Rao
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TE
Starzl
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Zeevi
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Thomson
D000938:Antigen-Presenting Cells / Q000187:drug effects*; D001854:Bone Marrow Cells; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor