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INFECTION AND IMMUNITY, Apr. 2005, p. 2184–2189 0019-9567/05/$08.00 0 doi:10.1128/IAI.73.4.2184–2189.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Vol. 73, No. 4
Effect of B7-2 and CD40 Signals from Activated Antigen-Presenting Cells on the Ability of Zwitterionic Polysaccharides To Induce T-Cell Stimulation
Tom Li Stephen,1† Marcus Niemeyer,2† Arthur O. Tzianabos,2 Martin Kroenke,1 Dennis L. Kasper,2,3 and Wiltrud M. Kalka-Moll1,2,4*
Institute for Medical Microbiology, Immunology and Hygiene,1 and First Department of Medicine,4 University of Cologne, Germany, and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital,2 and Department of Microbiology and Molecular Genetics,3 Harvard Medical School, Boston, Massachusetts
Received 3 September 2004/Accepted 25 October 2004
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 lowmolecular-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
Vol. 73, No. 4
Effect of B7-2 and CD40 Signals from Activated Antigen-Presenting Cells on the Ability of Zwitterionic Polysaccharides To Induce T-Cell Stimulation
Tom Li Stephen,1† Marcus Niemeyer,2† Arthur O. Tzianabos,2 Martin Kroenke,1 Dennis L. Kasper,2,3 and Wiltrud M. Kalka-Moll1,2,4*
Institute for Medical Microbiology, Immunology and Hygiene,1 and First Department of Medicine,4 University of Cologne, Germany, and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital,2 and Department of Microbiology and Molecular Genetics,3 Harvard Medical School, Boston, Massachusetts
Received 3 September 2004/Accepted 25 October 2004
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 lowmolecular-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
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