Regulation of the NK cell alloreactivity to bone marrow cells by the combination of the host NK gene complex and MHC haplotypes.
Host NK cells can reject MHC-incompatible (allogeneic) bone marrow cells (BMCs), suggesting their effective role for graft-vs leukemia effects in the clinical setting of bone marrow transplantation. NK cell-mediated rejection of allogeneic BMCs is dependent on donor and recipient MHC alleles and other factors that are not yet fully characterized. Whereas the molecular mechanisms of allogeneic MHC recognition by NK receptors have been well studied in vitro, guidelines to understand NK cell allogeneic reactivity under the control of multiple genetic components in vivo remain less well understood. In this study, we use congenic mice to show that BMC rejection is regulated by haplotypes of the NK gene complex (NKC) that encodes multiple NK cell receptors. Most importantly, host MHC differences modulated the NKC effect. Moreover, the NKC allelic differences also affected the outcome of hybrid resistance whereby F1 hybrid mice reject parental BMCs. Therefore, these data indicate that NK cell alloreactivity in vivo is dependent on the combination of the host NKC and MHC haplotypes. These data suggest that the NK cell self-tolerance process dynamically modulates the NK cell alloreactivity in vivo.
Iizuka
Koho
K
Department of Medicine, Rheumatology Division, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63310, USA. iizuk001@umn.edu
Scalzo
Anthony A
AA
Xian
Hong
H
Yokoyama
Wayne M
WM
D000483:Alleles; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics*; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D005810:Multigene Family / Q000276:immunology*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011971:Receptors, Immunologic / Q000235:genetics*; D055630:Receptors, NK Cell Lectin-Like; D017634:Self Tolerance / Q000235:genetics; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D000950:Antigens, Ly; D000954:Antigens, Surface; D006183:H-2 Antigens; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D001613:beta 2-Microglobulin