title: Effect of B7-2 and CD40 signals from activated antigen-presenting cells on the ability of zwitterionic polysaccharides to induce T-Cell stimulation.
abstract: Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria elicit potent CD4+-T-cell responses in vivo and in vitro. We demonstrated that HLA-DR on professional antigen-presenting cells (APCs) is required for ZPS-induced T-cell proliferation in vitro (15). Recently, it was shown that ZPSs are processed to low-molecular-weight carbohydrates by a nitric oxide-mediated mechanism in endosomes and locate in the major histocompatibility complex class II pathway (5, 15). The effect of the ZPS-mediated expression of HLA-DR and costimulatory molecules on the APC and T-cell engagement and subsequent T-cell activation has not been elucidated. Herein, we report that ZPS-mediated induction of HLA-DR-surface expression and T-cell proliferation are maximally enhanced after incubation of APCs for 8 h with ZPS. Treatment of APCs with bafilomycin A inhibits the up-regulation of ZPS-mediated HLA-DR surface expression and leads to inhibition of T-cell proliferation. Monoclonal antibodies (MAbs) to the costimulatory molecules B7-2 and CD40L specifically block ZPS-mediated T-cell activation, while a MAb to B7-1 does not. Surface expression of B7-2 and B7-1 but not of CD40 is maximally enhanced at 8 to 16 h of treatment of APCs with ZPS. The results demonstrate that the cellular immune response to ZPS depends on the translocation of HLA-DR to the cell surface and requires costimulation via B7-2 and CD40 on activated APCs. The implication is that activation of ZPS-specific T cells requires an orchestrated arrangement of both presenting and costimulatory molecules to form an immunological synapse.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical Center, Goldenfelsstr. 19-21, 50935 Cologne, Germany.
authors.forename: Tom Li
authors.initials: TL
authors.lastname: Stephen
authors.forename: Marcus
authors.initials: M
authors.lastname: Niemeyer
authors.forename: Arthur O
authors.initials: AO
authors.lastname: Tzianabos
authors.forename: Martin
authors.initials: M
authors.lastname: Kroenke
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kasper
authors.forename: Wiltrud M
authors.initials: WM
authors.lastname: Kalka-Moll
mesh_terms: D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000502:physiology*; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D011135:Polysaccharides, Bacterial; D023201:CD40 Ligand