In vivo studies of the maintenance of peripheral transplant tolerance after cyclosporine. Radiosensitive antigen-specific suppressor cells mediate lasting graft protection against primed effector cells.
Cellular mechanisms responsible for maintenance of peripheral transplant tolerance in a rodent model were evaluated. Donor-specific tolerance was established in ACI rats given a vascularized heterotopic cardiac allograft followed by a 10-day course of cyclosporine. Tolerance was associated with a reduction in donor-specific cytotoxic T lymphocyte precursors and the presence within the spleen of cells capable of transferring suppression in adoptive transfer assays. Experiments using thymectomized animals revealed that the establishment and maintenance of tolerance occurred peripherally, independently of the thymus. Adoptive transfer experiments demonstrated that ongoing graft tolerance was mediated by suppressor cells that were antigen-restricted, radiosensitive, and capable of preventing allograft rejection by naive as well as sensitized cells in vivo. Studies designed to disrupt tolerance demonstrated a remarkable durability of graft protection once established, and give insight into the identity and mechanism of action of suppressor cells generated in this model.
Nisco
S J
SJ
Department of Cardiothoracic Surgery, Stanford University School of Medicine, California 94305, USA.
Hissink
R J
RJ
Vriens
P W
PW
Hoyt
E G
EG
Reitz
B A
BA
Clayberger
C
C
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016913:Blood Component Transfusion; D016572:Cyclosporine / Q000627:therapeutic use*; D000939:Epitopes / Q000528:radiation effects; D006084:Graft Rejection / Q000532:radiotherapy; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000528:radiation effects; D008297:Male; D011846:Radio Waves; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013234:Stem Cells; D013602:T-Lymphocytes, Cytotoxic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000961:Antilymphocyte Serum; D000939:Epitopes; D007376:Interleukin-2; D016572:Cyclosporine