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Donor-Specific Regulatory T Cell-Mediated Immune Tolerance in an Intrahepatic Murine Allogeneic Islet Transplantation Model with Short-Term Anti-CD154 mAb Single Treatment
| Content Provider | SAGE Publishing |
|---|---|
| Author | Lee, Seok-Joo Kim, Hyun-Je Byun, Na-ri Park, Chung-Gyu |
| Copyright Year | 2020 |
| Abstract | Anti-CD154 blockade-based regimens remain unequaled in prolonging graft survival in various organ transplantation models. Several studies have focused on transplantation tolerance with the anti-CD154 blockade, but none of these studies has investigated the mechanisms associated with its use as the sole treatment in animal models, delaying our understanding of anti-CD154 blockade-mediated immune tolerance. The purpose of this study was to investigate the mechanism underlying the anti-CD154 monoclonal antibody (mAb) blockade in inducing immune tolerance using an intrahepatic murine allogeneic islet transplantation model. Allogeneic BALB/c AnHsd (BALB/c) islets were infused into the liver of diabetic C57BL/6 (B6) mice via the cecal vein. Anti-CD154 mAb (MR1) was administered on −1, 0, 1, 3, 5, and 7 d posttransplantation at 0.5 mg per mouse. We showed that short-term MR1 monotherapy could prolong the allogeneic islet grafts to more than 250 d in the murine intrahepatic islet transplantation model. The second islet grafts transplanted under the kidney capsule of the recipients were protected from rejection. We also found that rejection of same-donor skin grafts transplanted to the tolerant mice was modestly delayed. Using a DEREG mouse model, FoxP3+ regulatory T (Treg) cells were shown to play important roles in transplantation tolerance. In mixed lymphocyte reactions, Treg cells from the tolerant mice showed more potency in suppressing BALB/c splenocyte-stimulated Teff cell proliferation than those from naïve mice. In this study, we demonstrated for the first time that a short-term anti-CD154 mAb single treatment could induce FoxP3+ Treg cell-mediated immune tolerance in the intrahepatic murine allogeneic islet transplantation model. |
| Related Links | https://journals.sagepub.com/doi/pdf/10.1177/0963689720913876?download=true |
| ISSN | 09636897 |
| Volume Number | 29 |
| Journal | Cell Transplantation (CLL) |
| e-ISSN | 15553892 |
| DOI | 10.1177/0963689720913876 |
| Language | English |
| Publisher | Sage Publications CA |
| Publisher Date | 2020-03-27 |
| Publisher Place | Los Angeles |
| Access Restriction | Open |
| Rights Holder | © The Author(s) 2020 |
| Subject Keyword | liver islet transplantation anti-CD154 mAb (MR1) immune tolerance regulatory T cell |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Transplantation Biomedical Engineering |
