DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors
Open Access
- 24 November 2008
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 205 (13), 2965-2973
- https://doi.org/10.1084/jem.20081752
Abstract
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.This publication has 30 references indexed in Scilit:
- The Requirement for DNAM-1, NKG2D, and NKp46 in the Natural Killer Cell-Mediated Killing of Myeloma CellsCancer Research, 2007
- Activation, coactivation, and costimulation of resting human natural killer cellsImmunological Reviews, 2006
- Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptorBlood, 2006
- CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector FunctionsThe Journal of Immunology, 2005
- PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysisMolecular Immunology, 2005
- Natural Killer Cell-Mediated Killing of Freshly Isolated Neuroblastoma CellsCancer Research, 2004
- Cutting Edge: CD96 (Tactile) Promotes NK Cell-Target Cell Adhesion by Interacting with the Poliovirus Receptor (CD155)The Journal of Immunology, 2004
- Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)International Immunology, 2004
- Identification of PVR (CD155) and Nectin-2 (CD112) as Cell Surface Ligands for the Human DNAM-1 (CD226) Activating MoleculeThe Journal of Experimental Medicine, 2003
- DNAM-1, A Novel Adhesion Molecule Involved in the Cytolytic Function of T LymphocytesImmunity, 1996