A role for th2 cytokines in the suppression of CD8+ T cell-mediated graft rejection

Ralph Scully, Stephen P. Cobbold, Andrew L. Mellor, Martin Wissing, Bernd Arnold, Herman Waldmann

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

A major histocompatibility complex (MHC) class I-specific T cell receptor (TCR)-transgenic mouse was used to study classical-type transplantation tolerance in the adult. Engraftment of MHC class I-incompatible bone marrow and tolerance to donor-type skin grafts were obtained using dimethylmyeleran (DMM) as a myeloabiative agent and a non-depleting anti-CD8 monoclonal antibody (mAb) as the sole immunosuppressant. Surprisingly, bone marrow engraftment was facilitated by host CD4+ T cells, a subset normally considered unable to reject class I MHC-incompatible grafts. A combination of mAb to interleukins (IL)-4 and -10 antagonized the 'permissive' effects of host CD4+ T cells, indicating a possible role for Th2-type immunoregulation that can act on CD8+ T cells in this form of transplantation tolerance. The fate of graft-reactive T cells was monitored using anti-clonotypic antibodies. It was observed that bone marrow engraftment then led to peripheral deletion of mAb-blockaded, clonotype+ CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)1663-1670
Number of pages8
JournalEuropean Journal of Immunology
Volume27
Issue number7
DOIs
StatePublished - Jul 1 1997

Keywords

  • Bone marrow transplant
  • CD8 antibody
  • Immune regulation
  • T cell receptor transgenic
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Scully, R., Cobbold, S. P., Mellor, A. L., Wissing, M., Arnold, B., & Waldmann, H. (1997). A role for th2 cytokines in the suppression of CD8+ T cell-mediated graft rejection. European Journal of Immunology, 27(7), 1663-1670. https://doi.org/10.1002/eji.1830270711