Induction of donor-specific tolerance to rat cardiac and small bowel allografts by intrathymic inoculation of donor T-cells.
We have shown that donor-specific unresponsiveness to cardiac and islet allografts can be induced by intrathymic (IT) inoculation of uv-B-irradiated spleen cells or resting T-cells in the Lewis-to-ACI rat combination. To examine if tolerance to cardiac and small intestinal allografts can be induced in adult animals, we employed intrathymic inoculation of resting donor T-cells combined with sublethal total body irradiation of 200 rads on Day -7 relative to organ transplant and consistently induced permanent donor-specific cardiac allograft survival (> 300 days) and small bowel transplant (SBT) survival (> 100 days) in the Lewis-to-ACI rat combination. Similarly, IT inoculation of T-cells on Day -7 combined with 1 ml ALS on Days -7 and 0 relative to SBT resulted in indefinite donor-specific graft survival (> 100 days) in all recipients without any evidence of graft-versus-host disease (GVHD) in the high responder of Wistar-Furth (WF)-to-Lewis rat combination. In contrast, WF SBT was promptly rejected in recipients pretreated with intravenous administration of donor T-cells and ALS, thus confirming the privileged position of the thymus in the induction of tolerance. The long-term unresponsive ACI recipients challenged 150 days after cardiac transplant with a second-set graft specifically and permanently (> 120 days) accepted the second-set SBT without rejecting the primary cardiac grafts and without developing GVHD. Third-party grafts were rejected in a normal fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
Chowdhury
N C
NC
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Fawwaz
R A
RA
Oluwole
S F
SF
D000818:Animals; D006085:Graft Survival; D016027:Heart Transplantation; D007108:Immune Tolerance; D007116:Immunization, Passive; D007267:Injections; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000637:transplantation*; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D013601:T-Lymphocytes / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D013950:Thymus Gland / Q000502:physiology*; D014019:Tissue Donors; D014184:Transplantation, Homologous