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FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts
S J Knechtle1, D Vargo, J Fechner
1Department of Surgery, University of Wisconsin, Madison 53792, USA.
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.