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Function of NKG2D in natural killer cell–mediated rejection of mouse bone marrow grafts

Nature Immunology volume 6, pages 938–945 (2005)Cite this article

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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Figure 1: Rae-1 is expressed on BALB/c but not C57BL/6 bone marrow cells.
Figure 2: NKG2D blocks CB6F1 recipient rejection of BALB/c bone marrow.
Figure 3: NKG2D-independent rejection of C57BL/6 parental bone marrow grafts in CB6F1 recipients.
Figure 4: Rejection of syngeneic bone marrow cells expressing Rae-1.
Figure 5: Rejection of Rae-1ε-transgenic C57BL/6 bone marrow in DAP10-deficient and DAP12-deficient C57BL/6 recipients.
Figure 6: Impairment of bone marrow rejection in Rae-1ε-transgenic mice.

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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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Authors and Affiliations

  1. Department of Microbiology & Immunology and the Cancer Research Institute, University of California, San Francisco, 94143-0414, California, USA

    Kouetsu Ogasawara, Jonathan Benjamin, Rayna Takaki & Lewis L Lanier

  2. Department of Intractable Diseases, Division of Clinical Immunology, The Research Institute, International Medical Center of Japan, Toyama, Shinjuku-ku, 162-8655, Tokyo, Japan

    Kouetsu Ogasawara

  3. Biomedical Sciences Graduate Program, University of California, San Francisco, 94143-0414, California, USA

    Rayna Takaki

  4. Schering Plough BioPharma, Palo Alto, 94304, California, USA

    Joseph H Phillips

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  1. Kouetsu Ogasawara
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Correspondence to Lewis L Lanier.

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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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