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Infection and Immunity, February 2006, p. 1001-1008, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1001-1008.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Stimulation of CD8+ T Cells following Diphtheria Toxin-Mediated Antigen Delivery into Dendritic Cells

Christine A. Shaw and Michael N. Starnbach*

Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115

Received 3 August 2005/ Returned for modification 18 September 2005/ Accepted 8 November 2005

Recognition and clearance of many intracellular pathogens requires the activation and subsequent effector functions of CD8+ T lymphocytes. To stimulate CD8+ T cells by immunization, the target antigens must be delivered into the cytosol of host cells. There they can be processed into peptides and presented in the context of major histocompatibility complex class I molecules to antigen-specific CD8+ T cells. One method of delivering antigens into the cytosol is to fuse them to modified bacterial toxins that are able to enter mammalian cells. The expression pattern of the toxin receptors in the host will determine the cell population that the toxin fusion protein targets and will thus restrict antigen-specific T-cell recognition to the same population. In this study we describe the development and characterization of a diphtheria toxin (DT)-based antigen delivery system. Using CD11c-DTR transgenic mice that express the DT receptor in dendritic cells (DC), this system allows for targeted delivery of CD8+ T-cell antigen to DC. We show that antigen-specific CD8+ T cells proliferate in CD11c-DTR mice following immunization with catalytically inactive DT-antigen fusion proteins. We also show that a toxin-based system that restricts antigen delivery to DC results in more robust antigen-specific CD8+ T-cell proliferation than a toxin-based system that does not restrict delivery to a particular cell type. These results have implications for vaccine design, and they suggest that use of a toxin-based vector to target antigen to DC may be an effective way to induce a CD8+ T-cell response.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-1873. Fax: (617) 738-7664. E-mail: starnbach{at}hms.harvard.edu.

Editor: J. L. Flynn

Infection and Immunity, February 2006, p. 1001-1008, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1001-1008.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shaw, C. A., Starnbach, M. N. (2008). Both CD4+ and CD8+ T Cells Respond to Antigens Fused to Anthrax Lethal Toxin. Infect. Immun. 76: 2603-2611 [Abstract] [Full Text]  
  • Roan, N. R., Gierahn, T. M., Higgins, D. E., Starnbach, M. N. (2006). Monitoring the T cell response to genital tract infection. Proc. Natl. Acad. Sci. USA 103: 12069-12074 [Abstract] [Full Text]  


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