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Published 7 June 2004. doi:10.1084/jem.20031111
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 11, 1595-1605
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Tumor Rejection Induced by CD70-mediated Quantitative and Qualitative Effects on Effector CD8+ T Cell Formation

Ramon Arens1,2, Koen Schepers3, Martijn A. Nolte1,2, Michiel F. van Oosterwijk1,2, René A.W. van Lier1, Ton N.M. Schumacher3, and Marinus H.J. van Oers2

1 Laboratory for Experimental Immunology and 2 Department of Hematology, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, Netherlands
3 Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands

Address correspondence to Rene A.W. van Lier, Laboratory for Experimental Immunology, L1-152, Academic Medical Center, University of Amsterdam, P.O. Box 22700, Meibergdreef 15, 1100 DD Amsterdam, Netherlands. Phone: 31-20-5666063; Fax: 31-20-5669756; email: r.vanlier{at}amc.uva.nl

In vivo priming of antigen-specific CD8+ T cells results in their expansion and differentiation into effector T cells followed by contraction into a memory T cell population that can be maintained for life. Recent evidence suggests that after initial antigenic stimulation, the magnitude and kinetics of the CD8+ T cell response are programmed. However, it is unclear to what extent CD8+ T cell instruction in vivo is modulated by costimulatory signals. Here, we demonstrate that constitutive ligation of the tumor necrosis factor receptor family member CD27 by its ligand CD70 quantitatively augments CD8+ T cell responses to influenza virus infection and EL-4 tumor challenge in vivo by incrementing initial expansion and maintaining higher numbers of antigen-specific T cells in the memory phase. Concomitantly, the quality of antigen-specific T cells improved as evidenced by increased interferon (IFN)-{gamma} production and a greater cytotoxic potential on a per cell basis. As an apparent consequence, the superior effector T cell formation induced by CD70 protected against a lethal dose of poorly immunogenic EL4 tumor cells in a CD8+ T cell– and IFN-{gamma}–dependent manner. Thus, CD70 costimulation enhances both the expansion and per cell activity of antigen-specific CD8+ T cells.

Key Words: costimulation • influenza virus • tumor immunity • MHC tetramer • TNF family member

The online version of this article contains supplemental material.

Abbreviations used in this paper: CFSE, carboxyfluorescein succinimidyl ester; DLN, draining LN; GFP, green fluorescent protein; MFI, mean fluorescence intensity; NP, nucleoprotein; Tg, transgenic.


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