Primate renal transplants using immunotoxin.
BACKGROUND
T-lymphocyte depletion 7 days before transplantation with immunotoxin FN 18-CRM9 has resulted in tolerance to subsequent renal allografts. We tested the effect of giving immunotoxin on the day of the transplantation and evaluated its effect on rhesus monkey and allograft survival, on antibody production, and on T-cell recovery.


METHODS
Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys. Immunotoxin was given starting on the day of transplantation, with and without prednisone and mycophenolate mofetil for 3 days. T-cell subsets and alloantibody levels were measured by flow cytometry. The ability of treated monkeys to develop antibody to tetanus, diphtheria, and xenoantibody was measured. Histology of renal transplants was read in a blinded manner.


RESULTS
Immunotoxin started on the day of transplantation resulted in prolonged allograft survival in all treatment groups. Graft loss between days 50 and 135 was most often due to interstitial nephritis. Later graft loss was due to chronic rejection. Monkeys had intact antibody responses to alloantigen, tetanus, diphtheria, and xenoantibody. Their CD4 cells recovered gradually over 6 months.


CONCLUSIONS
Immunotoxin reliably prolongs renal allograft survival when started on the day of transplantation, but interstitial nephritis and chronic rejection limit the development of long-term tolerance. T-cell-dependent B-cell responses remain intact after treatment.
Knechtle
S J
SJ
Department of Surgery, University of Wisconsin, Madison, USA.
Fechner
J H
JH
Dong
Y
Y
Stavrou
S
S
Neville
D M
DM
Oberley
T
T
Buckley
P
P
Armstrong
N
N
Rusterholz
K
K
Hong
X
X
Tsuchida
M
M
Hamawy
M M
MM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D000922:Immunotoxins / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods*; D008253:Macaca mulatta; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007074:Immunoglobulin G; D000922:Immunotoxins; D013745:Tetanus Toxoid