Ex Vivo Expanded Donor Alloreactive Regulatory T Cells Lose Immunoregulatory, Proliferation, and Antiapoptotic Markers After Infusion Into ATG-lymphodepleted, Nonhuman Primate Heart Allograft Recipients
| Autor: | Helong Dai, Kazuki Sasaki, Lien Lu, Hong Zhang, Angelica Perez-Gutierrez, Alan F. Zahorchak, Mohamed Ezzelarab, Jay K. Bhama, Angus W. Thomson, Dirk J. van der Windt |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Graft Rejection
Male Adoptive cell transfer Time Factors Regulatory T cell T cell Apoptosis chemical and pharmacologic phenomena 030230 surgery Lymphocyte Activation T-Lymphocytes Regulatory Lymphocyte Depletion Article 03 medical and health sciences 0302 clinical medicine Antigen Animals Medicine Cells Cultured Antilymphocyte Serum Cell Proliferation Transplantation business.industry Graft Survival FOXP3 Adoptive Transfer Tacrolimus Disease Models Animal Macaca fascicularis Phenotype medicine.anatomical_structure Immunology Heart Transplantation 030211 gastroenterology & hepatology Apoptosis Regulatory Proteins business Ex vivo |
| Zdroj: | Transplantation |
| ISSN: | 0041-1337 |
| Popis: | BACKGROUND Regulatory T cell (Treg) therapy is a promising approach to amelioration of allograft rejection and promotion of organ transplant tolerance. However, the fate of infused Treg, and how this relates to their therapeutic efficacy using different immunosuppressive regimens is poorly understood. Our aim was to analyze the tissue distribution, persistence, replicative activity and phenotypic stability of autologous, donor antigen alloreactive Treg (darTreg) in anti-thymocyte globulin (ATG)-lymphodepleted, heart-allografted cynomolgus monkeys. METHODS darTreg were expanded ex vivo from flow-sorted, circulating Treg using activated donor B cells and infused posttransplant into recipients of major histocompatibility complex-mismatched heart allografts. Fluorochrome-labeled darTreg were identified and characterized in peripheral blood, lymphoid, and nonlymphoid tissues and the graft by flow cytometric analysis. RESULTS darTreg selectively suppressed autologous T cell responses to donor antigens in vitro. However, following their adoptive transfer after transplantation, graft survival was not prolonged. Early (within 2 wk posttransplant; under ATG, tacrolimus, and anti-IL-6R) or delayed (6-8 wk posttransplant; under rapamycin) darTreg infusion resulted in a rapid decline in transferred darTreg in peripheral blood. Following their early or delayed infusion, labeled cells were evident in lymphoid and nonlymphoid organs and the graft at low percentages ( |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|