Intrathymic transplantation of donor cells allows a stabilized, incompatible renal transplant to survive indefinitely after cyclosporine withdrawal.
Recent experiments have shown that exposure of maturing rat thymocytes to donor cells induces a condition of donor-specific unresponsiveness in the recipient that allows indefinite survival of a subsequent kidney transplant without the need for long-term immunosuppressants. Here, studies were performed in Lewis (RT1(1)) rats to determine whether (a) the process of unresponsiveness to kidney allograft induced by intrathymic donor cell inoculation occurred also with a noninbred strain of donor animals, and (b) this technique could allow the elimination of the need for daily immunosuppressive therapy in animals already transplanted with an incompatible kidney. Kidneys from noninbred Sprague-Dawley rats transplanted in incompatible Lewis (RT1(1)) rats, previously injected intrathymically with cells from the same donor, survived indefinitely. Intrathymic inoculation of donor cells into Lewis rats allowed a stabilized, incompatible renal allograft from Brown-Norway (RT1n) rats to survive indefinitely after discontinuation of immunosuppressive treatment with cyclosporine. These findings provide an approach for renal transplantation without immunosuppressive therapy and a potential strategy to overcome side effects related to the use of immunosuppressants in animals already transplanted.
Perico
N
N
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Rossini
M
M
Imberti
O
O
Bontempelli
M
M
Remuzzi
G
G
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage; D006085:Graft Survival / Q000276:immunology; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000276:immunology*; D014184:Transplantation, Homologous
D016572:Cyclosporine