Journal
SCIENCE
Volume 295, Issue 5562, Pages 2094-2097Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1068438
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Funding
- NIDDK NIH HHS [R01 DK54767] Funding Source: Medline
- NINDS NIH HHS [P01 NS27405] Funding Source: Medline
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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.
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