RT info:eu-repo/semantics/article
T1 Porcine Islet-Specific Tolerance Induced by the Combination of Anti-LFA-1 and Anti-CD154 mAbs is Dependent on PD-1
A1 Arefanian, Hossein
A1 Tredget, Eric B.
A1 Mok, Dereck C. M.
A1 Ramji, Qahir
A1 Rafati, Shahin
A1 Rodríguez Barbosa, José Ignacio
A1 Korbutt, Gregory S.
A1 Rajotte, Ray V.
A1 Gill, Ron G.
A1 Rayat, Gina R.
A2 Sanidad Animal
K1 Veterinaria
K1 Islet xenograft
K1 Species-specific tolerance
K1 Tissue-specific tolerance
K1 PD-1/PD-1L pathway
K1 Monoclonal antibody (mAb)
K1 3109 Ciencias Veterinarias
K1 3104.08 Porcinos
AB [EN]We previously demonstrated that short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) induces tolerance to neonatal porcine islet (NPI) xenografts that is mediated by regulatory T cells (Tregs) in B6 mice. In this study, we examined whether the coinhibitory molecule PD-1 is required for the induction and maintenance of tolerance to NPI xenografts. We also determined whether tolerance to NPI xenografts could be extended to allogeneic mouse or xenogeneic rat islet grafts since we previously demonstrated that tolerance to NPI xenografts could be extended to second-party NPI xenografts. Finally, we determined whether tolerance to NPI xenografts could be extended to allogeneic mouse or second-party porcine skin grafts. Diabetic B6 mice were transplanted with 2,000 NPIs under the kidney capsule and treated with short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs. Some of these mice were also treated simultaneously with anti-PD-1 mAb at >150 days posttransplantation. Spleen cells from some of the tolerant B6 mice were used for proliferation assays or were injected into B6 rag−/− mice with established islet grafts from allogeneic or xenogeneic donors. All B6 mice treated with anti-LFA-1 and anti-CD154 mAbs achieved and maintained normoglycemia until the end of the study; however, some mice that were treated with anti-PD-1 mAb became diabetic. All B6 rag−/− mouse recipients of first- and second-party NPIs maintained normoglycemia after reconstitution with spleen cells from tolerant B6 mice, while all B6 rag−/− mouse recipients of allogeneic mouse or xenogeneic rat islets rejected their grafts after cell reconstitution. Tolerant B6 mice rejected their allogeneic mouse or xenogeneic second-party porcine skin grafts while remaining normoglycemic until the end of the study. These results show that porcine islet-specific tolerance is dependent on PD-1, which could not be extended to skin grafts.
PB SAGE Publication
SN 0963-6897
LK https://hdl.handle.net/10612/19896
UL https://hdl.handle.net/10612/19896
NO Arefanian, H., Tredget, E. B., Mok, D. C. M., Ramji, Q., Rafati, S., Rodriguez-Barbosa, J., Korbutt, G. S., Rajotte, R. V., Gill, R. G., & Rayat, G. R. (2016). Porcine islet-specific tolerance induced by the combination of anti-LFA-1 and anti-CD154 mabs is dependent on PD-1. Cell Transplantation, 25(2), 327-342. https://doi.org/10.3727/096368915X688506
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 03-jun-2024