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* Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland;
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239; and
Institute for Virology, Heinrich-Heine-University, Düsseldorf, Germany
The dynamics of mouse cytomegalovirus (MCMV)-specific CD4 T cell responses and the mechanisms by which these cells contribute to viral control are not well understood, mainly due to lack of appropriate tools to characterize MCMV-specific CD4 T cells. We therefore generated MCMV-specific CD4 T cell hybridomas, then used an MCMV expression library and overlapping peptides to identify CD4 T cell epitopes. We used these novel tools to study the long-term kinetics and organ distribution of MCMV-specific CD4 T cells in comparison to MCMV-specific CD8 T cell responses. We demonstrate that the overall MCMV-specific CD4 T cell response stabilizes during the latent stage, which stands in contrast to subpopulations of MCMV-specific CD8 T cells and HCMV-specific CD4 T cells which accumulate over the course of CMV latency. Furthermore, MCMV-specific CD4 T cells displayed a Th1 phenotype, secreting high levels of IFN-
and TNF-
and to some extent IL-2, cytokines which are involved in protection from CMV disease.
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 This work was supported by the Roche Research Fund for Biology, the Eidgenössiche Technische Hochschule Zurich, Deutsche Forschungsgemeinschaft He 2526/7-1, the Swiss National Science Foundation, the Roche Research Foundation, the Vontobel Foundation, and the European Molecular Biology Organization Young Investigator Programme.
2 Address correspondence and reprint requests to Dr. Annette Oxenius, Swiss Federal Institute of Technology, Institute for Microbiology, Eidgenössische Technische Hochschule Zurich, Wolfgang-Pauli-Strasse 10, HCI G401, 8093 Zurich, Switzerland. E-mail address: oxenius{at}micro.biol.ethz.ch
3 Abbreviations used in this paper: MCMV, mouse CMV; ORF, open reading frame; HCMV, human CMV; BAC, bacterial artificial chromosome; MEF, mouse embryonic fibroblast; wt, wild type; FLP, protein encoded by the FLP gene of the 2-micron plasmid of yeast.
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