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. In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance. OBJECTIVE: 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. FUTURE DIRECTIONS This reagent holds enormous promise for immunosuppression in clinical transplantation. KEY WORDS MHC, tolerance, transplantation

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000167-38
Application #
6277727
Study Section
Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
38
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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