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Influence of SHIP on the NK Repertoire and Allogeneic Bone Marrow Transplantation

Science  15 Mar 2002:
Vol. 295, Issue 5562, pp. 2094-2097
DOI: 10.1126/science.1068438

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Abstract

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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: kerrw{at}moffitt.usf.edu

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