Tolerance induced by anti-CD3 immunotoxin plus 15-deoxyspergualin associates with donor-specific indirect pathway unresponsiveness.
Peritransplant treatment with anti-CD3 immunotoxin plus deoxyspergualin induces tolerance to kidney allografts in most rhesus macaque recipients. Tolerant recipients maintain normal function for years without evidence of chronic rejection. Indirect alloantigen presentation is implicated in chronic rejection. Accordingly, we determined if anti-CD3 immunotoxin plus deoxyspergualin induced rejection-free tolerance associates with suppression of anti-donor indirect pathway responses. Tolerant recipients exhibited an early decrease in direct anti-donor responses with recovery to baseline levels by 3 years posttransplantation. In contrast, tolerant monkeys were unresponsive to donor antigens presented by the indirect pathway. Recipients that rejected their allografts retained vigorous direct and indirect anti-donor responses. Therefore, following temporary donor-specific hyporesponsiveness, direct responses recover in tolerant recipients >1.5 years after transplantation. However, tolerant recipients tested at 1.9-4 years posttransplant are specifically unresponsive to donor antigens presented by the indirect pathway. Thus, the rejection-free state of tolerant recipients may depend on mechanisms regulating indirect pathway responsiveness.
Asiedu
Clement K
CK
Division of Transplant Immunology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Dong
Sai S
SS
Lobashevsky
Andrew
A
Jenkins
Stacie M
SM
Thomas
Judith M
JM
D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006146:Guanidines / Q000494:pharmacology*; D006648:Histocompatibility; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D000922:Immunotoxins / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008253:Macaca mulatta; D008297:Male; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000276:immunology
D017252:CD3 Complex; D006146:Guanidines; D007166:Immunosuppressive Agents; D000922:Immunotoxins; C037258:gusperimus