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The Journal of Immunology, 2003, 171: 2995-3002.
Copyright © 2003 by The American Association of Immunologists

In Vivo Impact of CpG1826 Oligodeoxynucleotide on CD8 T Cell Primary Responses and Survival 1

Laurent Beloeil*, Martine Tomkowiak*, Georgi Angelov*, Thierry Walzer2,*, Patrice Dubois3,{dagger} and Jacqueline Marvel3,4,*

* Centre d’Etude et de Recherche en Virologie et en Immunologie, Unité 503, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Lyon, France; and {dagger} GlaxoSmithKline Biologicals, Rixensart, Belgium

CpG oligodeoxynucleotide (ODN) promotes maturation of APCs in vivo and induces strong type 1 T cell responses in mice. In this study, we have investigated the ability of CpG1826 to modulate peptide-specific CD8 T cell responses in a context where CD4 T cells are likely to play a minor role. The effects of CpG1826 were evaluated in a system where a population of NP68-specific F5 TCR transgenic CD8 T cells is diluted into a polyclonal host following adoptive transfer into C57BL/10 syngeneic recipients. Using this approach, we found that CpG1826 enhanced the ability of F5 CD8 T cells to undergo multiple divisions in vivo, to express IFN-{gamma} ex vivo, and to up-regulate memory-associated cell surface markers such as CD122 (IL-2R{beta}) and Ly-6C. Moreover, CpG1826 greatly increased in vivo cytotoxic activity. Using tetramer detection, we found that CpG1826 promoted long-term survival of Ag-specific CD8 T cells after immunization while no NP68-specific cells were detected when the cognate peptide was injected alone. These results indicate that CpG1826 acts as an adjuvant which increases CD8 T cell effector responses and promotes long-term survival of NP68 peptide-specific cells in vivo. They also suggest that this adjuvant can modulate CD8 T cell responses in a system which is likely to be independent of CD4 T cell help.




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