New method for thyroid transplantation across major histocompatibility complex barriers using allogeneic bone marrow transplantation.
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.
Lee
S
S
First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
Sugiura
K
K
Nagahama
T
T
Iwai
H
H
Yasumizu
R
R
Yamashita
T
T
Ikehara
S
S
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000627:therapeutic use; D006085:Graft Survival; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D019653:Myeloablative Agonists / Q000627:therapeutic use; D009439:Neuraminidase / Q000627:therapeutic use; D016377:Organ Transplantation / Q000379:methods*; D013154:Spleen / Q000473:pathology; D013961:Thyroid Gland / Q000637:transplantation*; D018183:Transplantation Chimera; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D019653:Myeloablative Agonists; D009439:Neuraminidase; D002066:Busulfan