Influence of SHIP on the NK repertoire and allogeneic bone marrow transplantation.
Natural killer cell (NK) receptors for major histocompatibility complex (MHC) class I influence engraftment and graft-versus-tumor effects after allogeneic bone marrow transplantation. We find that SH2-containing inositol phosphatase (SHIP) influences the repertoire of NK receptors. In adult SHIP-/- mice, the NK compartment is dominated by cells that express two inhibitory receptors capable of binding either self or allogeneic MHC ligands. This promiscuous repertoire has significant functional consequences, because SHIP-/- mice fail to reject fully mismatched allogeneic marrow grafts and show enhanced survival after such transplants. Thus, SHIP plays an important role in two processes that limit the success of allogeneic marrow transplantation: graft rejection and graft-versus-host disease.
Wang
Jia-Wang
JW
Immunology Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
Howson
Julie M
JM
Ghansah
Tomar
T
Desponts
Caroline
C
Ninos
John M
JM
May
Sarah L
SL
Nguyen
Kim H T
KH
Toyama-Sorimachi
Noriko
N
Kerr
William G
WG
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000950:Antigens, Ly; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002470:Cell Survival; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008024:Ligands; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011971:Receptors, Immunologic / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction; D014184:Transplantation, Homologous; D018909:src Homology Domains
D015703:Antigens, CD; D000950:Antigens, Ly; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D019869:Phosphatidylinositol 3-Kinases; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; C098706:INPPL1 protein, human