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Exacerbated graft-versus-host disease in Pirb−/− mice

Nature Immunology volume 5, pages 623–629 (2004)Cite this article

Abstract

Immune responses are often regulated by opposing receptor pairs that recognize the same ligand but deliver either activating or inhibitory signals. Paired immunoglobulin-like receptors (PIRs) expressed on B cells and myeloid cells comprise a major histocompatibility complex class I recognition system that regulates the responsiveness of these cells. Here, activating PIR-A and inhibitory PIR-B bound various mouse major histocompatibility complex class I (H-2) molecules, and in vitro H-2 tetramer stimulation of PIR-B on B cells or PIR-A on macrophages induced intracellular phosphotyrosine signaling. After transfer of allogeneic splenocytes into PIR-B-deficient mice, the mice showed exacerbated graft-versus-host disease, which was due to augmented activation of recipient dendritic cells with concomitant upregulation of PIR-A and increased interferon-γ production. PIR-A-induced dendritic cell activation also led to increased proliferation of donor cytotoxic T cells. Thus, PIR-A and PIR-B are counteracting receptors that are essential for successful tissue transplantation and may regulate irrelevant reaction to autologous tissues in a constitutive way in physiological conditions.

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Figure 1: Biosensor analyses of the interaction between the rPIR-B ectodomain and MHC class I molecules.
Figure 2: H-2 tetramer binds to PIR-B on splenic B cells and PIR-A on peritoneal macrophages.
Figure 3: PIR-B and PIR-A can initiate tyrosine-based cell signaling after H-2 binding.
Figure 4: Induction of lethal GVHD in Pirb−/− mice.
Figure 5: Activated recipient DCs during GVHD show upregulated expression of PIR-A and PIR-B.

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Acknowledgements

We thank H. Kubagawa and M.D. Cooper for 6C1 hybridoma. Supported by the Core Research for Evolutional Science and Technology program of the Japan Science and Technology Agency; a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Virtual Research Institute of Aging of Nippon Boehringer Ingelheim; and the Center of Excellence program Center for Innovative Therapeutic Development Towards the Conquest of Signal Transduction Diseases.

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  1. Department of Experimental Immunology and Core Research for Evolutional Science and Technology program of Japan Science and Technology Agency, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai, 980-8575, Japan

    Akira Nakamura, Eiji Kobayashi & Toshiyuki Takai

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Correspondence to Toshiyuki Takai.

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Nakamura, A., Kobayashi, E. & Takai, T. Exacerbated graft-versus-host disease in Pirb−/− mice. Nat Immunol 5, 623–629 (2004). https://doi.org/10.1038/ni1074

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