Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor

• Published in: Blood Vol. 107; no. 4; pp. 1491 - 1496
• Main Authors: Tahara-Hanaoka, Satoko, Shibuya, Kazuko, Kai, Hirayasu, Miyamoto, Akitomo, Morikawa, Yoshihiro, Ohkochi, Nobuhiro, Honda, Shin-ichiro, Shibuya, Akira
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.02.2006; American Society of Hematology; The Americain Society of Hematology
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - immunology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunologic Memory; Ligands; Membrane Proteins - immunology; Mice; Mice, Inbred C57BL; Modulation of the immune response (stimulation, suppression); Neoplasms - immunology; Receptors, Virus - immunology; Antineoplastic agent; Dendritic cell; Ligand; Rodentia; Cell adhesion molecule; Natural immunity; Immune regulation; Malignant tumor; Natural killer cell; Vertebrata; Mammalia; Mouse; Animal; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-04-1684

The poliovirus receptor CD155 and its family member CD112 (nectin-2) are the ligands for the activating cell-surface receptor DNAM-1 on CD8+ T cells and natural killer (NK) cells. Here, we demonstrate that, whereas the RMA tumor grew in syngeneic mice, DNAM-1 ligand-transduced RMA was rejected, in which CD8+ T cells and NK cells played an essential role. Importantly, CD8+ memory cytotoxic T cells to parental RMA were generated in these mice. We found that DNAM-1 was also expressed on CD8α+, rather than CD8α-, dendritic cells (DCs). Cross-linking DNAM-1 induced maturation of CD8α+ DCs. Antigen presentation by these stimulated DCs drove Th1 cells. Moreover, the rejection of DNAM-1 ligand-transduced RMA was canceled in CD4+ T-cell–depleted and major histocompatibility complex class II–deficient mice. Taken together, these results suggest that DNAM-1 ligands stimulate innate immunity by CD8α+ DCs as well as NK cells, which efficiently prime cell-mediated tumor-specific immunity.