Premium
Production of granulocyte–macrophage colony‐stimulating factor by T cells is regulated by B7 and IL‐1β
Author(s) -
KRUGER M.,
VAN GOOL S.,
PENG X. H.,
COOREVITS L.,
CASTEELSVAN DAELE M.,
CEUPPENS J. L.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-643.x
Subject(s) - granulocyte macrophage colony stimulating factor , interleukin 3 , biology , cd28 , microbiology and biotechnology , cd80 , cd40 , cytokine , antigen presenting cell , t cell , immunology , cytotoxic t cell , immune system , in vitro , biochemistry
Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) has proliferation‐ and differentiation‐inducing effects on immature myeloid cells in the bone marrow, and it can modulate the function of several types of mature myeloid cells. We have stimulated purified human T cells with immobilized anti‐CD3 or mitogenic anti‐CD2 (a combination of monoclonal antibodies 9‐1 and 9.6) which could induce GM‐CSF production. The cytokines interleukin‐1β (IL‐1β) and IL‐2 strongly enhanced GM‐CSF production, while IL‐4, IL‐6, GM‐CSF, interferon‐γ (IFN‐γ) and tumour necrosis factor (TNF) had no effect. Activation of protein kinase C by phorbol myristate acetate or triggering of CD28 on T cells by monoclonal antibody 9.3 provided accessory signals for enhanced GM‐CSF production in activated T cells. Most important, the addition of mouse cells transfected with human B7‐1 (CD80), a natural ligand for CD28, provided a potent accessory signal for GM‐CSF production by activated T cells, which could not be blocked by cyclosporin A. The effect of IL‐1β was in fact indirect, and resulted from enhanced IL‐2 production, while the effect of B7 resulted from both IL‐2‐dependent and IL‐2‐independent pathways. We conclude that antigen‐presenting cells (APC) can up‐regulate GM‐CSF production through IL‐1β and through CD28 triggering by B7 molecules. As GM‐CSF itself up‐regulates B7 expression and IL‐1β production by APC, a bidirectional regulatory feedback pathway between APC and T cells seems to modulate GM‐CSF production.