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Infection and Immunity, April 2005, p. 2184-2189, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2184-2189.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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,{dagger} Marcus Niemeyer,2,{dagger} 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 First Department of Medicine, University of Cologne, Germany,4 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital,2 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts3

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 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.

* Corresponding author. Mailing address: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical Center, Goldenfelsstr. 19-21, 50935 Cologne, Germany. Phone: 49 221 478 7650. Fax: 49 221 478 86004. E-mail: Wiltrud.Kalka-Moll{at}medizin.uni-koeln.de.

Editor: J. N. Weiser

{dagger} T.L.S. and M. N. contributed equally to the present study.

Infection and Immunity, April 2005, p. 2184-2189, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2184-2189.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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