The Journal of Experimental Medicine
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Published online November 24, 2008
doi:10.1084/jem.20081752
The Journal of Experimental Medicine, Vol. 205, No. 13, 2965-2973
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Gilfillan et al.
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BRIEF DEFINITIVE REPORT

DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors

Susan Gilfillan1, Christopher J. Chan2, Marina Cella1, Nicole M. Haynes2, Aaron S. Rapaport1, Kent S. Boles1, Daniel M. Andrews2, Mark J. Smyth2, and Marco Colonna1

1 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110
2 Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, 3002 Victoria, Australia

CORRESPONDENCE Marco Colonna: mcolonna{at}pathology.wustl.edu

Natural killer (NK) cells and CD8 T cells require adhesion molecules for migration, activation, expansion, differentiation, and effector functions. DNAX accessory molecule 1 (DNAM-1), an adhesion molecule belonging to the immunoglobulin superfamily, promotes many of these functions in vitro. However, because NK cells and CD8 T cells express multiple adhesion molecules, it is unclear whether DNAM-1 has a unique function or is effectively redundant in vivo. To address this question, we generated mice lacking DNAM-1 and evaluated DNAM-1–deficient CD8 T cell and NK cell function in vitro and in vivo. Our results demonstrate that CD8 T cells require DNAM-1 for co-stimulation when recognizing antigen presented by nonprofessional antigen-presenting cells; in contrast, DNAM-1 is dispensable when dendritic cells present the antigen. Similarly, NK cells require DNAM-1 for the elimination of tumor cells that are comparatively resistant to NK cell–mediated cytotoxicity caused by the paucity of other NK cell–activating ligands. We conclude that DNAM-1 serves to extend the range of target cells that can activate CD8 T cell and NK cells and, hence, may be essential for immunosurveillance against tumors and/or viruses that evade recognition by other activating or accessory molecules.


S. Gilfillan, C.J. Chan, M.J. Smyth, and M. Colonna contributed equally to this paper.

© 2008 Gilfillan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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