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Kinetic and Mechanistic Requirements for Helping CD8 T Cells¹

Paola Agnellini^*, Melanie Wiesel^*, Katrin Schwarz, Petra Wolint^*, Martin F. Bachmann and Annette Oxenius^2,*

^* Swiss Federal Institute of Technology, Institute for Microbiology, Zurich, Switzerland; and Cytos Biotechnology AG, Zurich-Schlieren, Switzerland

The requirements for the generation of fully competent long-lived memory CD8 T cells and in particular the role and the mechanisms of help from CD4 T cells remain ill-defined. Memory CD8 T cells generated in the absence of CD4 T cell help often have an impaired recall proliferation and are thus unable to confer protection against certain pathogens. However, the timing and the mechanisms involved in the delivery of help are still unclear and differ between various experimental systems. In this study, we investigated the role of CD4 T help in generating memory CD8 T cells in a defined heterologous prime-boost system, consisting of priming with replication incompetent virus-like particles and challenge with recombinant vaccinia virus, both sharing only a common lymphocytic choriomeningitis virus-derived CD8 T cell epitope. We show in this system that delivery of help is only essential during the challenge phase for recall proliferation of memory CD8 T cells. Furthermore, we show that generation of proliferation-competent memory CD8 T cells is independent of CD40 and CCR5 and that in vivo IL-2 supplementation neither during priming nor during challenge was able to rescue recall proliferation of "unhelped" memory CD8 T cells.

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 Research Fund for Biology, Eidgenössische Technische Hochschule Zürich, Swiss National Science Foundation, and Vontobel Foundation.

² Address correspondence and reprint requests to Dr. Annette Oxenius, Swiss Federal Institute of Technology, Institute for Microbiology, Eidgenössische Technische Hochschule Hönggerberg, Wolfgang-Pauli-Strasse 10, HCI G401, 8093 Zurich, Switzerland. E-mail address: oxenius{at}micro.biol.ethz.ch

³ Abbreviations used in this paper: CD40L, CD40 ligand; DC, dendritic cell; VLP, virus-like particle; VVG2, vaccinia virus G2; LCMV, lymphocytic choriomeningitis virus; RT, room temperature.

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