FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts.
BACKGROUND
Transplant tolerance, rather than immunity, may be favored in the setting of a lower mature lymphoid mass in the recipient induced by anti-T cell agents. A novel immunosuppressive agent, FN18-CRM9, known to specifically kill T cells with great potency, was evaluated in a transplant model.


METHODS
In order to ablate recipient T cells, the immunotoxin FN18-CRM9 was administered to rhesus monkey recipients of MHC-mismatched renal allografts. Donor lymphocytes were injected intrathymically into some animals.


RESULTS
All monkeys with T-cell depletion by immunotoxin had prolonged allograft survival, and tolerance confirmed by skin grafting has been confirmed in five of six long-surviving recipients.


CONCLUSIONS
In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance.
Knechtle
S J
SJ
Department of Surgery, University of Wisconsin, Madison 53792, USA.
Vargo
D
D
Fechner
J
J
Zhai
Y
Y
Wang
J
J
Hanaway
M J
MJ
Scharff
J
J
Hu
H
H
Knapp
L
L
Watkins
D
D
Neville
D M
DM
D000818:Animals; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D000922:Immunotoxins / Q000494:pharmacology*; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D000922:Immunotoxins