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* Clinic for Immunology and Rheumatology and
Institute of Virology, Hannover Medical School, Hannover, Germany
Dendritic cells (DC), which can be subdivided into different phenotypic and functional subsets, play a pivotal role in the generation of cytotoxic T cell immunity against viral infections. Understanding the modes of Ag acquisition, processing and presentation by DC is essential for the design of effective antiviral vaccines. We aimed to assess the contribution of direct vs cross-presentation for the induction of HSV1-specific CD8+ T lymphocyte responses in mice. Using HSV1 strains expressing fluorescence proteins, we provide evidence for the ability of HSV1 to induce viral transcription. Using HSV1-wild-type as well as gB- or gH-deficient mutants to either directly inoculate DC or to infect target cells, which then were given to DC, we show that DC acquired viral Ag via phagocytosis of target cells and via direct inoculation of virus being released from target cells. Our study corroborates the function of the CD8+ DC specialized in Ag cross-presentation and confirms this specific feature for Ags that these DC acquire directly from HSV1. However, although infection of cross-presenting DC amplified T cell responses, it was not a requirement for presentation of viral Ags, both in vitro and in vivo. Finally, we provide evidence that direct presentation did not contribute to the Ag presentation capacity of CD8+ DC after phagocytosis of infected target cells. We conclude that cross-presentation is of major importance for the induction of CTL immunity in mice.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 A.C.J. was supported by a fellowship from the Deutscher Akademischer Austauschdienst and the Hannover Biomedical Research School. C.-H.N., C.B., and B.S. were supported by the German Research Council (Deutsche Forschungsgemeinschaft Grants So403/2 and So403/3). G.M.N.B. was supported by a grant from the Excellence Cluster "From Regenerative Biology to reconstructive Therapy" and Collaborative Research Grant Sonderforschungsbereich 587 (German Research Foundation).
2 Address correspondence and reprint requests to Dr. Georg M. N. Behrens, Clinic for Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail address: behrens.georg{at}mh-hannover.de
3 Abbreviations used in this paper: DC, dendritic cell; ONPG, o-nitrophenyl-β-D-galactosylpyranoside; BAC, bacterial artificial chromosome; wt, wild type; ORF, open reading frame; MOI, multiplicity of infection; RFP, red fluorescent protein; CAV, cell-associated virus; CCD, cytochalasin D; HVEM, herpesvirus entry mediator.
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  H. Constabel, M. V. Stankov, C. Hartwig, T. Tschernig, and G. M. N. Behrens Impaired Lung Dendritic Cell Migration and T Cell Stimulation Induced by Immunostimulatory Oligonucleotides Contribute to Reduced Allergic Airway Inflammation J. Immunol., September 1, 2009; 183(5): 3443 - 3453. [Abstract] [Full Text] [PDF]
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