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.
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.
Authors: I Koyama; O Nadazdin; S Boskovic; T Ochiai; R N Smith; M Sykes; H Sogawa; T Murakami; T B Strom; R B Colvin; D H Sachs; G Benichou; A B Cosimi; T Kawai Journal: Am J Transplant Date: 2007-02-07 Impact factor: 8.086
Authors: A D Kirk; D M Harlan; N N Armstrong; T A Davis; Y Dong; G S Gray; X Hong; D Thomas; J H Fechner; S J Knechtle Journal: Proc Natl Acad Sci U S A Date: 1997-08-05 Impact factor: 11.205
Authors: Phuong-Thu T Pham; Gerald S Lipshutz; Phuong-Truc T Pham; Joseph Kawahji; Jennifer S Singer; Phuong-Chi T Pham Journal: Drug Des Devel Ther Date: 2009-09-21 Impact factor: 4.162