title: Blocking B7 and CD40 co-stimulatory molecules decreases antiviral T cell activity.
abstract: Inhibition of co-stimulatory signals for T cells by interrupting CD80/CD86-CD28 and CD40-CD154 interactions is a promising approach to prevent transplant rejection and to induce graft tolerance. However, this tolerizing treatment might affect T cell reactivity towards all the antigens to which the immune system is exposed during treatment. We addressed the question whether such inhibition of co-stimulatory ligands on human antigen presenting cells (APC) would affect T cell reactivity against a virus. This was tested in an in vitro system with freshly isolated human monocytes transduced with adenovirus (ad) containing either murine interferon-gamma (mIFN-gamma) or green fluorescent protein (GFP) as marker transgene. T cells co-cultured with transduced monocytes proliferated and produced cytokines. These 'primed' T cells had strong antiviral activity as they subsequently killed ad/GFP-transduced monocytes and reduced mIFN-gamma accumulation in coculture with ad/mIFN-transduced monocytes. However, if priming had occurred in the presence of blocking anti-CD40/CD80/CD86 MoAbs, generation of this antiviral activity was completely prevented. Moreover, T cells primed in the absence of co-stimulatory cells failed to proliferate upon restimulation with adenovirus-transduced monocytes. The results confirm that co-stimulatory signals from APC are required for efficient induction of antiviral T cell activity and point to a potential infectious risk of blocking co-stimulatory signals.
authors.affiliation: Laboratory of Experimental Immunology, Catholic University of Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vermeiren
authors.forename: J L
authors.initials: JL
authors.lastname: Ceuppens
authors.forename: H
authors.initials: H
authors.lastname: Haegel-Kronenberger
authors.forename: M
authors.initials: M
authors.lastname: De Boer
authors.forename: L
authors.initials: L
authors.lastname: Boon
authors.forename: S W
authors.initials: SW
authors.lastname: Van Gool
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000328:Adult; D019138:Antibodies, Blocking / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D015415:Biomarkers / Q000032:analysis; D019013:CD40 Antigens / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007202:Indicators and Reagents / Q000032:analysis; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D008164:Luminescent Proteins / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods; D019076:Transgenes / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015415:Biomarkers; D019013:CD40 Antigens; C497964:CD86 protein, human; D007202:Indicators and Reagents; D018793:Interleukin-13; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma