Veto cell suppression mechanisms in the prevention of allograft rejection.
Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy. Veto suppression prevents the generation of antigen-specific T-helper and cytotoxic T lymphocytes in vitro provided that the T-lymphocyte precursors specifically recognize antigenic peptides associated with the major histocompatibility complex molecules class II and class I, respectively, expressed on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.
Jacobsen
I M
IM
Department of Medical Anatomy, Panum Institute, University of Copenhagen, Denmark.
Claesson
M H
MH
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera; D006084:Graft Rejection / Q000517:prevention & control*; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015395:Histocompatibility Antigens Class I