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Murine Models

A two-phase pathogenesis of graft-versus-host disease in mice

Bone Marrow Transplantation volume 29, pages 151–158 (2002)Cite this article

Abstract

Activation of donor T cells is required for the development of graft-versus-host disease (GVHD), a major complication of bone marrow transplantation. We investigated a murine model of GVHD across major and minor histocompatibility barriers. BALB/c recipients were lethally irradiated and transplanted with 107 bone marrow and 5 × 106 spleen cells from C57BL/6 donors. There were two separate phases of clinical disease. The first phase was most severe on day 7 after transplant. Weight and condition improved until day 12 and then a second phase of clinical GVHD commenced, which persisted until euthanasia. IL-2 mRNA expression, as a measure of T cell activation, was determined by quantitative PCR. The two phases of clinical GVHD were preceded by two separate peaks of IL-2 mRNA in the spleen. Host MHC class II+ cells became undetectable by flow cytometry 7 days after transplantation, whereas donor MHC class II+ cells increased during the first 9 days after transplantation. Removal of donor MHC class II+ cells from the graft had no effect on the first phase. Possible roles for host and donor antigen-presenting cells (APC) in the two phases of the disease are discussed.

Bone Marrow Transplantation (2002) 29, 151–158. doi:10.1038/sj.bmt.1703328

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Acknowledgements

We thank Dr Phil Hodgkin for helpful discussion. This work was supported by the Arrow Foundation, the Kanematsu Memorial Award, an Australian Postgraduate Award to LvL, and an infrastructure grant from the NSW Health Department.

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Author notes

  1. K Atkinson

    Present address: Center for Cellular Therapy, American Red Cross, Rosslyn, VA, USA

Authors and Affiliations

  1. Department of Haematology, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia

    L van Leeuwen, A Guiffre & K Atkinson

  2. Department of Anatomical Pathology, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia

    SP Rainer

  3. Centre for Immunology, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia

    WA Sewell

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  1. L van Leeuwen
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  2. A Guiffre
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van Leeuwen, L., Guiffre, A., Atkinson, K. et al. A two-phase pathogenesis of graft-versus-host disease in mice. Bone Marrow Transplant 29, 151–158 (2002). https://doi.org/10.1038/sj.bmt.1703328

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