PMID- 11579314 OWN - NLM STAT- MEDLINE DCOM- 20011018 LR - 20190713 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 72 IP - 6 DP - 2001 Sep 27 TI - New method for thyroid transplantation across major histocompatibility complex barriers using allogeneic bone marrow transplantation. PG - 1144-9 AB - BACKGROUND: It has been shown that allogeneic bone marrow transplantation (BMT) after lethal irradiation elicits donor-specific tolerance for organ or tissue transplantation across major histocompatibility complex (MHC) barriers. Recently, we have demonstrated that the portal venous (p.v.) administration of donor bone marrow cells (BMCs) elicits donor-specific tolerance across MHC barriers by only two administrations of an immunosuppressant (CsA or FK-506). In our study, using the central and intrahepatic tolerance-inducing system, we have established a new method for thyroid transplantation with BMT that would be more applicable to humans. METHODS: In addition to sublethal (6-5 Gy) irradiation, recipient B6 (H-2b) mice received injections i.p. with the myeloablative drug busulfan (BU) on day -2 to provide a sufficient "space" for the donor hematopoietic cells to expand in the recipients. To induce the intrahepatic tolerance, donor BALB/c (H-2d) BMCs were treated with neuraminidase (Neu), which enhances the trapping of i.v. injected BMCs in the liver. After the injection of Neu-treated BMCs, the thyroid organs from the BALB/c mice were engrafted under the renal capsules. RESULTS: A 90% graft survival rate was obtained over 100 days by a combination of BU administration, 6 Gy irradiation, and i.v. injection of Neu-treated BMCs [BU+6 Gy+(Neu) i.v.], and a 70% graft survival rate was obtained by [BU+5 Gy+(Neu) i.v.]. However, the graft survival rate significantly decreased when either the BU or Neu treatment was omitted. T cells collected from the tolerant recipients suppressed the proliferative responses to donor alloantigens. CONCLUSIONS: Using both BU and Neu treatments, we have succeeded in inducing long-term tolerance and preventing the rejection of thyroid allografts by the single-day protocol. FAU - Lee, S AU - Lee S AD - First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. FAU - Sugiura, K AU - Sugiura K FAU - Nagahama, T AU - Nagahama T FAU - Iwai, H AU - Iwai H FAU - Yasumizu, R AU - Yasumizu R FAU - Yamashita, T AU - Yamashita T FAU - Ikehara, S AU - Ikehara S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Myeloablative Agonists) RN - EC 3.2.1.18 (Neuraminidase) RN - G1LN9045DK (Busulfan) SB - IM MH - Animals MH - Bone Marrow Cells/drug effects MH - *Bone Marrow Transplantation MH - Busulfan/therapeutic use MH - Graft Survival MH - Lymphocyte Culture Test, Mixed MH - *Major Histocompatibility Complex MH - Mice MH - Mice, Inbred Strains MH - Myeloablative Agonists/therapeutic use MH - Neuraminidase/therapeutic use MH - Organ Transplantation/*methods MH - Spleen/pathology MH - Thyroid Gland/*transplantation MH - Transplantation Chimera MH - *Transplantation Immunology MH - Transplantation, Homologous EDAT- 2001/10/02 10:00 MHDA- 2001/10/19 10:01 CRDT- 2001/10/02 10:00 PHST- 2001/10/02 10:00 [pubmed] PHST- 2001/10/19 10:01 [medline] PHST- 2001/10/02 10:00 [entrez] AID - 10.1097/00007890-200109270-00027 [doi] PST - ppublish SO - Transplantation. 2001 Sep 27;72(6):1144-9. doi: 10.1097/00007890-200109270-00027.