PMID- 1641776 OWN - NLM STAT- MEDLINE DCOM- 19920828 LR - 20100324 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 112 IP - 2 DP - 1992 Aug TI - Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow. PG - 370-6; discussion 376-7 AB - BACKGROUND: Induction of donor-specific tolerance to tissue or organ allografts can readily be achieved by administration of allogeneic bone marrow to neonatal rodents; however, in adult recipients induction of transplantation tolerance by this strategy generally requires intensive cytoablative conditioning. Described here is a novel method of promoting transplantation tolerance that involves inoculation of donor bone marrow into the thymus of transiently immunosuppressed adult recipients. METHODS: Prospective Wistar-Furth recipients were inoculated with allogeneic Lewis bone marrow cells (BMCs) either intrathymically or intravenously in conjunction with a single dose of antilymphocyte serum 2 to 3 weeks before receiving donor-strain cardiac allografts. Recipients were monitored for graft survival and examined for presence of hematopoietic chimerism. RESULTS: Intrathymic but not intravenous inoculation of donor BMCs led to permanent survival of donor-strain cardiac allografts, whereas third-party Dark agouti cardiac allografts were rejected promptly. Persistence of donor chimerism was demonstrated in the thymus of Wistar-Furth recipients of intrathymic Lewis BMCs for as long as 3 weeks after BMC inoculation. CONCLUSIONS: Intrathymic inoculation of BMCs concurrently with a single dose of antilymphocyte serum induces donor-specific unresponsiveness to rat cardiac allografts. The unresponsiveness may be the result of deletion or functional inactivation of alloreactive clones maturing in a thymus bearing donor alloantigen. Intrathymic inoculation of BMCs deserves further evaluation as a possible clinical strategy for the induction of transplantation tolerance. FAU - Odorico, J S AU - Odorico JS AD - Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104. FAU - Barker, C F AU - Barker CF FAU - Posselt, A M AU - Posselt AM FAU - Naji, A AU - Naji A LA - eng GR - DK34878/DK/NIDDK NIH HHS/United States GR - DK44309/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Surgery JT - Surgery JID - 0417347 SB - IM MH - Animals MH - Bone Marrow Cells MH - *Bone Marrow Transplantation MH - Graft Survival MH - *Heart Transplantation MH - *Immune Tolerance MH - Injections MH - Male MH - Rats MH - Rats, Inbred Lew MH - Rats, Inbred WF MH - *Thymus Gland/cytology MH - *Tissue Donors MH - Transplantation, Homologous EDAT- 1992/08/01 00:00 MHDA- 1992/08/01 00:01 CRDT- 1992/08/01 00:00 PHST- 1992/08/01 00:00 [pubmed] PHST- 1992/08/01 00:01 [medline] PHST- 1992/08/01 00:00 [entrez] AID - 0039-6060(92)90233-P [pii] PST - ppublish SO - Surgery. 1992 Aug;112(2):370-6; discussion 376-7.