Application of cyclophosphamide-induced tolerance in α1,3-galactosyltransferase knockout mice presensitized with Galα1-3Galβ-4-GlcNAc antigens
| Autor: | Tatsushi Onzuka, Shinji Okano, I Shimizu, Ryuji Tominaga, Yukihiro Tomita, Toshiro Iwai |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Transplantation Conditioning Transplantation Heterotopic Cyclophosphamide T-Lymphocytes α1 3 galactosyltransferase Organ transplantation Epitopes Mice Antigen Immune Tolerance medicine Animals Mice Knockout Galactosyltransferase B-Lymphocytes Mice Inbred BALB C Transplantation Chimera business.industry Graft Survival Skin Transplantation General Medicine Galactosyltransferases Tolerance induction Antibody Formation Knockout mouse Immunology Heart Transplantation Female Immunization Surgery Rabbits business Trisaccharides Immunosuppressive Agents Spleen medicine.drug Natural antibody |
| Zdroj: | Surgery Today. 38:807-814 |
| ISSN: | 1436-2813 0941-1291 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink