Two-signal requirement for activation and effector function of natural killer cell response to allogeneic tumor cells.
Optimal activation of T cells requires delivery of both antigenic and costimulatory signals. It is unclear, however, if the function of the natural killer (NK) cells is also modulated by these 2 signals. Here we report that efficient control of solid allogeneic tumors by NK cells depends on codelivery of both B7-1 and major histocompatibility complex (MHC) class I on the tumor cells. The codelivery is required for optimal expansion and effector function of NK cells in response to both melanoma and plasmocytoma that expressed allogeneic MHC class I. Our results demonstrate that the 2 signals required for T-cell function also can regulate NK immunity and reveal an important similarity between the innate NK response and the adaptive T-cell response.
Gao
Jian-Xin
JX
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210, USA.
Liu
Xingluo
X
Wen
Jing
J
Caligiuri
Michael A
MA
Stroynowski
Iwona
I
Zheng
Pan
P
Liu
Yang
Y
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010954:Plasmacytoma / Q000276:immunology / Q000473:pathology; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000950:Antigens, Ly; D018122:B7-1 Antigen; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D037181:Lectins, C-Type; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins; C489516:Tap2 protein, mouse