Application of cyclophosphamide-induced tolerance in alpha1,3-galactosyltransferase knockout mice presensitized with Gal alpha 1-3Gal beta-4-GlcNAc antigens.
Surg Today
; 38(9): 807-14, 2008.
Article
en En
| MEDLINE
| ID: mdl-18751946
ABSTRACT
PURPOSE:
Hyperacute rejection (HAR) mediated by the natural antibody (nAb) against Gal alpha 1-3Gal beta-4-GlcNAc (alpha Gal) is the major obstacle in xenogeneic organ transplantation. Previously, we reported the acceptance of donor heart grafts in anti-alpha Gal nAb-producing galactosyltransferase knockout (GalT KO) mice after cyclophosphamide (CP)-induced tolerance conditioning. In the present study, we applied our tolerance induction conditioning in presensitized recipient mice.METHODS:
GalT KO (alpha Gal(-/-), H-2(b/d)) recipient mice were presensitized with alpha Gal(+) rabbit red blood cells (RRBCs). Presensitized or nonsensitized recipient mice were treated with CP-induced tolerance conditioning, consisting of AKR (alpha Gal(+/+), H-2(k)) spleen cells (SC), CP, busulfan (BU), and AKR bone marrow cells (BMC). We assessed the survival of donor hearts and skin grafts and analyzed the production of anti-alpha Gal Abs by flow cytometry.RESULTS:
Donor mixed chimerism was achieved in the presensitized GalT KO mice treated with CP-induced tolerance conditioning. In parallel with the disappearance of anti-alpha Gal Abs, permanent acceptance of donor heart grafts and skin grafts was observed in presensitized and GalT KO mice treated with CP-induced tolerance conditioning.CONCLUSIONS:
Both B-cell and T-cell tolerance was achieved in the presence of a higher titer of anti-alpha Gal Abs after treatment with CP-induced tolerance conditioning.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trisacáridos
/
Acondicionamiento Pretrasplante
/
Ciclofosfamida
/
Galactosiltransferasas
/
Supervivencia de Injerto
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Tolerancia Inmunológica
/
Epítopos
Límite:
Animals
Idioma:
En
Revista:
Surg Today
Año:
2008
Tipo del documento:
Article
País de afiliación:
Japón