Autologous graft-vs-host disease: mechanisms and potential therapeutic effect

Bone Marrow Transplant. 1993:12 Suppl 3:S65-9.

Abstract

Administration of the immunosuppressive drug cyclosporine (CsA) after autologous or syngeneic bone marrow transplantation (BMT) elicits an autoimmune syndrome with pathology identical to graft-vs-host disease (GVHD). This syndrome can be induced both in man and in rats and is associated with the development of cytolytic autoreactive T cells that recognize MHC class II determinants. Studies in a rat model suggest that there are two essential components necessary for the induction of an autologous/syngeneic GVHD and include the inhibition of thymic dependent clonal deletion of autoreactive T lymphocytes by CsA and the elimination of a peripheral regulatory mechanism by the preparative regimen. The absence of peripheral autoregulation creates a permissive environment for the activation of the autoreactive T cells. Based on our understanding of the immunobiology of this autoimmune syndrome, we have utilized the induction of autologous/syngeneic GVHD in an attempt to provide an antitumor therapeutic effect after autologous BMT. Interim analyses of our clinical trials suggest that this approach is quite promising.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Bone Marrow Transplantation / immunology
  • Bone Marrow Transplantation / pathology
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use
  • Disease Models, Animal
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Rats
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Transplantation, Autologous / physiology

Substances

  • Histocompatibility Antigens Class II
  • Cyclosporine