Production of granulocyte-macrophage colony-stimulating factor by T cells is regulated by B7 and IL-1 beta.
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-1 beta (IL-1 beta) and IL-2 strongly enhanced GM-CSF production, while IL-4, IL-6, GM-CSF, interferon-gamma (IFN-gamma) 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-1 beta 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-1 beta and through CD28 triggering by B7 molecules. As GM-CSF itself up-regulates B7 expression and IL-1 beta production by APC, a bidirectional regulatory feedback pathway between APC and T cells seems to modulate GM-CSF production.
Kruger
M
M
Department of Pathophysiology, Catholic University of Leuven, Belgium.
Van Gool
S
S
Peng
X H
XH
Coorevits
L
L
Casteels-Van Daele
M
M
Ceuppens
J L
JL
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005246:Feedback; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor