title: Differential modulation of B7-1 and B7-2 isoform expression on human monocytes by cytokines which influence the development of T helper cell phenotype.
abstract: The co-stimulatory molecules B7-1/B7-2 expressed on the surface of antigen-presenting cells have been suggested to influence the development of T helper 1 (Th1)-versus Th2-immune responses. These studies were conducted to elucidate the effect of immunoregulatory cytokines which influence the development of Th1/Th2 immune responses on the expression of the B7 isoforms B7-1 and B7-2 on resting and activated human monocytes and B cells. Interleukin (IL)-4 and IL-10, which induce the development of Th2 immune responses, down-regulated B7-2 and moderately up-regulated B7-1 expression on resting CD14+ monocytes in peripheral blood mononuclear cells. Interferon-gamma (IFN-gamma), which induces the development of Th1 immune responses, enhanced the expression of both B7-1 and B7-2 isoforms. Tumor necrosis factor (TNF)-alpha, which elicits both Th1- and Th2 characteristics depending on experimental conditions, down-regulated B7-2 but did not alter B7-1 expression. The effect of TNF-alpha and B7-2 expression is not mediated through endogenously produced IL-10, as addition of anti-IL-10 antibodies did not restore B7-2 expression. None of the other cytokines tested, including IL-1 alpha, IL-1 beta, IL-2, IL-5, IL-6, IL-12, granulocyte/macrophage colony-stimulating factor (GM-CSF), and transforming growth factor (TGF)-alpha, modulated the expression of B7 isoforms on resting monocytes. Lipoolysaccharide stimulation of monocytes down-regulated B7-2 and up-regulated B7-1 expression in a manner similar to IL-10. The expression of B7-1 and B7-2 on purified B cells were not altered by any of the cytokines tested, including IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IFN-gamma, TNF-alpha, TGF-alpha and GM-CSF. Taken together, our results suggest that the cytokines which induce Th1/Th2 immune responses exert differential effects on B7 isoform expression on resting monocytes but have no effect on resting or activated B cells.
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada.
authors.forename: W D
authors.initials: WD
authors.lastname: Creery
authors.forename: F
authors.initials: F
authors.lastname: Diaz-Mitoma
authors.forename: L
authors.initials: L
authors.lastname: Filion
authors.forename: A
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins