Abstract
Irradiation-resistant natural killer (NK) cells in an F1 recipient can reject parental bone marrow, and host NK cells can also prevent engraftment of allogeneic bone marrow. We show here that repopulating bone marrow cells in certain mouse strains expressed retinoic acid early inducible 1 proteins, which are ligands for the activating NKG2D NK cell receptor. Treatment with a neutralizing antibody to NKG2D prevented rejection of parental BALB/c bone marrow in (C57BL/6 × BALB/c) F1 recipients and allowed engraftment of allogeneic BALB.B bone marrow in C57BL/6 recipients. Additionally, bone marrow from C57BL/6 mice transgenic for retinoic acid early inducible 1ε was rejected by syngeneic mice but was accepted after treatment with antibody to NKG2D. If other stem cells or tissues upregulate expression of NKG2D ligands after transplantation, NKG2D may contribute to graft rejection in immunocompetent hosts.
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Acknowledgements
We thank N. Killeen and J. Dietrich of the University of California, San Francisco Comprehensive Cancer Center Transgenic and Targeted Mutagenesis Shared Resource for the generation of Rae-1ε-transgenic mice; all Lanier lab members for technical assistance and discussions; and T. Sasazuki for discussions. Supported by the National Institutes of Health (CA95137), the Human Frontier Science Program (K.O.), the Uehara Memorial Foundation (K.O.), the Irvington Institute Foundation (K.O.), the University of California, San Francisco Liver Center (P30-DK26743 to K.O.) and the American Cancer Society (L.L.L.).
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These studies were supported in part by Schering Plough BioPharma.
Supplementary information
Supplementary Fig. 1
NKG2D mAb CX5 does not deplete NK cells in vivo. (PDF 417 kb)
Supplementary Fig. 2
H-2 incompatibility is not required for NKG2D-dependent BM rejection. (PDF 49 kb)
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Ogasawara, K., Benjamin, J., Takaki, R. et al. Function of NKG2D in natural killer cell–mediated rejection of mouse bone marrow grafts. Nat Immunol 6, 938–945 (2005). https://doi.org/10.1038/ni1236
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DOI: https://doi.org/10.1038/ni1236
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