Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor.
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 CD8alpha+, rather than CD8alpha-, dendritic cells (DCs). Cross-linking DNAM-1 induced maturation of CD8alpha+ 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 CD8alpha+ DCs as well as NK cells, which efficiently prime cell-mediated tumor-specific immunity.
Tahara-Hanaoka
Satoko
S
Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Ten-nodai, Tsukuba, Ibaraki 305-8575, Japan.
Shibuya
Kazuko
K
Kai
Hirayasu
H
Miyamoto
Akitomo
A
Morikawa
Yoshihiro
Y
Ohkochi
Nobuhiro
N
Honda
Shin-ichiro
S
Shibuya
Akira
A
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007156:Immunologic Memory; D008024:Ligands; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D011991:Receptors, Virus / Q000276:immunology*; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D008024:Ligands; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor