Differential migration of passenger leukocytes and rapid deletion of naive alloreactive CD8 T cells after mouse liver transplantation

Authors

  • Szun S. Tay,

    1. Liver Immunology Group, Centenary Institute, Newtown, Australia
    2. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
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    • These authors contributed equally to this work.These authors are equal last authors.

  • Bo Lu,

    1. Immunology Research Centre, St. Vincent's Hospital, Melbourne, Australia
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    • These authors contributed equally to this work.These authors are equal last authors.

  • Fred Sierro,

    1. Liver Immunology Group, Centenary Institute, Newtown, Australia
    2. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
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  • Volker Benseler,

    1. Liver Immunology Group, Centenary Institute, Newtown, Australia
    2. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
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  • Claire M. McGuffog,

    1. Liver Immunology Group, Centenary Institute, Newtown, Australia
    2. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
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  • G. Alex Bishop,

    1. Collaborative Transplantation Research Group, Bosch Institute, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
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  • Peter J. Cowan,

    1. Immunology Research Centre, St. Vincent's Hospital, Melbourne, Australia
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  • Geoffrey W. McCaughan,

    1. Liver Immunology Group, Centenary Institute, Newtown, Australia
    2. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
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  • Karen M. Dwyer,

    1. Immunology Research Centre, St. Vincent's Hospital, Melbourne, Australia
    2. Department of Medicine, University of Melbourne, Melbourne, Australia
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  • David G. Bowen,

    Corresponding author
    1. Liver Immunology Group, Centenary Institute, Newtown, Australia
    2. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
    3. Collaborative Transplantation Research Group, Bosch Institute, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
    • Address reprint requests to David G. Bowen, Ph.D., M.D., Liver Immunology Group, Centenary Institute, Locked Bag No. 6, Newtown, New South Wales 2042, Australia. Telephone: + 61 2 95656264; FAX: +61 2 95656101; E-mail: d.bowen@centenary.org.auAddress reprint requests to Patrick Bertolino, Ph.D., Liver Immunology Group, Centenary Institute, Locked Bag No. 6, Newtown, New South Wales 2042, Australia. Telephone: +61 2 95656186; FAX: +61 2 95656101; E-mail: p.bertolino@centenary.org.au

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  • Patrick Bertolino

    Corresponding author
    1. Liver Immunology Group, Centenary Institute, Newtown, Australia
    2. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
    • Address reprint requests to David G. Bowen, Ph.D., M.D., Liver Immunology Group, Centenary Institute, Locked Bag No. 6, Newtown, New South Wales 2042, Australia. Telephone: + 61 2 95656264; FAX: +61 2 95656101; E-mail: d.bowen@centenary.org.auAddress reprint requests to Patrick Bertolino, Ph.D., Liver Immunology Group, Centenary Institute, Locked Bag No. 6, Newtown, New South Wales 2042, Australia. Telephone: +61 2 95656186; FAX: +61 2 95656101; E-mail: p.bertolino@centenary.org.au

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Abstract

Donor passenger leukocytes (PLs) from transplanted livers migrate to recipient lymphoid tissues, where they are thought to induce the deletion of donor-specific T cells and tolerance. Difficulties in tracking alloreactive T cells and PLs in rats and in performing this complex surgery in mice have limited progress in identifying the contribution of PL subsets and sites and the kinetics of T cell deletion. Here we developed a mouse liver transplant model in which PLs, recipient cells, and a reporter population of transgenic CD8 T cells specific for the graft could be easily distinguished and quantified in allografts and recipient organs by flow cytometry. All PL subsets circulated rapidly via the blood as soon as 1.5 hours after transplantation. By 24 hours, PLs were distributed differently in the lymph nodes and spleen, whereas donor natural killer and natural killer T cells remained in the liver and blood. Reporter T cells were activated in both liver and lymphoid tissues, but their numbers dramatically decreased within the first 48 hours. These results provide the first unequivocal demonstration of the differential recirculation of liver PL subsets after transplantation, and show that alloreactive CD8 T cells are deleted more rapidly than initially reported. This model will be useful for dissecting early events leading to the spontaneous acceptance of liver transplants. Liver Transpl 19:1224–1235, 2013. © 2013 AASLD.

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