Wang Jia-Wang, Howson Julie M, Ghansah Tomar, Desponts Caroline, Ninos John M, May Sarah L, Nguyen Kim H T, Toyama-Sorimachi Noriko, Kerr William G
Immunology Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
Science. 2002 Mar 15;295(5562):2094-7. doi: 10.1126/science.1068438.
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.
主要组织相容性复合体（MHC）I类分子的自然杀伤细胞（NK）受体影响异基因骨髓移植后的植入及移植物抗肿瘤效应。我们发现，含SH2结构域的肌醇磷酸酶（SHIP）影响NK受体库。在成年SHIP基因敲除小鼠中，NK细胞库主要由表达两种能够结合自身或异基因MHC配体的抑制性受体的细胞组成。这种混杂的受体库具有显著的功能后果，因为SHIP基因敲除小鼠无法完全排斥完全不匹配的异基因骨髓移植物，并且在此类移植后存活率提高。因此，SHIP在限制异基因骨髓移植成功的两个过程中发挥重要作用：移植物排斥和移植物抗宿主病。
