Soluble CD23 directly activates monocytes to contribute to the antigen-independent stimulation of resting T cells.
The majority of T cells at the site of an inflammatory lesion do not appear to be Ag-specific, but they still contribute to the inflammatory response. Herein, we report that sCD23 activates monocytes to participate in the stimulation of resting T cells in the absence of TCR engagement. First, sCD23 selectively triggers monokine release by purified monocytes in the absence of costimulus. It induces TNF-alpha, IL-1 beta, IL-8, granulocyte-macrophage-CSF, and prostaglandin E2 but no IL-10, IL-12, TGF-beta, or leukotriene B4. The sCD23-induced TNF-alpha production is significantly inhibited by IL-4 and IL-10 but not by TGF-beta. Also, monocytes activated by sCD23 express decreased levels of HLA-DR and increased levels of CD14, CD54, CD40, and B7 Ag. Next, we show that, in the presence of monocytes, sCD23 is a potent costimulator of IL-2 or IL-12-induced IFN-gamma production by resting T cells in the absence of exogenous Ag and that this effect is partially reduced by anti-TNF-alpha mAb. B cells cannot substitute for monocytes, and CD4+ and CD8+ T cells are equal responders. The data further indicate that monocyte-T cell contact, more particularly CD40-CD40L interactions, is required for IFN-gamma production in response to IL-2 plus sCD23, and the response to IL-12 plus sCD23 is CD40- and B7-independent but is still partially contact-dependent. It is proposed that sCD23, when produced locally at a site of immune response, may trigger an inflammatory process via monokine release and may further amplify it via the stimulation of bystander non-Ag-specific T cells.
Armant
M
M
University of Montreal, Louis-Charles Simard Research Center, Quebec, Canada.
Rubio
M
M
Delespesse
G
G
Sarfati
M
M
D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D015846:Monokines / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D015846:Monokines; D011948:Receptors, Antigen, T-Cell; D017455:Receptors, IgE; D007371:Interferon-gamma