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Related Experiment Videos

T cell suppression in transplantation tolerance through linked recognition

J D Davies1, L Y Leong, A Mellor

  • 1Department of Biology and Cancer Center, University of California San Diego, La Jolla, 92093-0063, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 15, 1996
PubMed
Summary

Inducing immunologic tolerance in mice can lead to indefinite acceptance of allogeneic tissues. This study reveals that suppression mechanisms, potentially acting locally, can extend tolerance to new antigens through linked recognition.

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Area of Science:

  • Immunology
  • Transplantation Biology
  • Tolerogenic Mechanisms

Background:

  • Allogeneic tissue grafts are often accepted indefinitely in mice treated with CD4- and CD8-specific antibodies, indicating induced immunologic tolerance.
  • While tolerance to minor histocompatibility antigens is established, some third-party grafts are unexpectedly accepted or rejected slowly, suggesting complex suppressive mechanisms.

Purpose of the Study:

  • To investigate the hypothesis that accepted third-party grafts share antigens with the original tolerizing graft, making them targets for suppressive CD4+ T cells.
  • To elucidate the role of linked recognition in the suppression of graft rejection within a tolerized host.

Main Methods:

  • Mice were tolerized to a specific set of minor antigens (B10 minors).
  • Tolerized mice were challenged with third-party grafts expressing these B10 minors plus a strong transplantation antigen (H-2Kb).

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  • The effect of linking the H-2Kb antigen to the B10 minors on an F1 graft was assessed for rejection rates.

    • Main Results:

    • Grafts containing both the original minor antigens and the H-2Kb antigen were significantly less rejected in tolerized mice compared to naive mice.
    • Rejection of the third-party graft was impaired when the strong transplantation antigen was "linked" to the previously tolerated minor antigens.
    • Suppression appears to operate locally, possibly on the same antigen-presenting cell, via a mechanism of linked recognition.

    Conclusions:

    • Suppression of transplant rejection in tolerized mice can operate locally through linked recognition of antigens.
    • Linked recognition of antigens may extend immunologic tolerance to previously non-tolerized third-party antigens.