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Immunological unresponsiveness induced by recipient cells transfected with donor MHC genes

Nature volume 332, pages 161–164 (1988)Cite this article

Abstract

Immunological unresponsiveness to allografts can be achieved by pretreating recipients with cells (whole blood, erythrocytes, lymphocytes) expressing donor-specific histocompatibility antigens1. Attempts to determine the relative contribution of class I or class II major histocompatibility antigens and/or minor histocompatibility (miH) antigens towards the induction of an unresponsive state have yielded conflicting results2–10. We have addressed this issue using DNA-mediated gene transfer to introduce murine class I or class II major histocompatibility complex (MHC) genes from the organ donor into cells of recipient origin. This allowed murine recipients of cardiac allografts to be pretreated with syngeneic cells sharing only an isolated class I or class II MHC locus product with the donor organ. We show that pretreatment with either donor class I or class II antigens prolongs survival of cardiac allografts, and that the capacity of a particular donor MHC antigen to induce unresponsiveness is the product of its intrinsic immunogenicity and the antigen load delivered during pretreatment. These results explain discrepancies in earlier studies of antigen-induced unresponsiveness and suggest a novel approach to specific immunosup-pression in clinical transplantation.

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Author notes

  1. Riccardo A. Superina

    Present address: Department of Surgery, Hospital for Sick Children, Toronto, Ontario

  2. Kathryn J. Wood: To whom correspondence should be addressed.

Affiliations

  1. Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Joren C. Madsen, Riccardo A. Superina, Kathryn J. Wood & Peter J. Morris

Authors
  1. Joren C. Madsen
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  2. Riccardo A. Superina
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  3. Kathryn J. Wood
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  4. Peter J. Morris
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Madsen, J., Superina, R., Wood, K. et al. Immunological unresponsiveness induced by recipient cells transfected with donor MHC genes. Nature 332, 161–164 (1988). https://doi.org/10.1038/332161a0

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