1. Combined treatment with vitamin D3 and antibody agents suppresses secondary heart transplant rejection in the early postoperative period.
- Author
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Xie B, Ma Y, Xi Y, Di A, Chen X, Chen Y, Zhang L, Xu S, Wang C, Yan G, and Qi Z
- Subjects
- Animals, Drug Therapy, Combination, Female, Forkhead Transcription Factors metabolism, Graft Rejection etiology, Graft Survival, Humans, Immunologic Memory, Immunosuppression Therapy, Intercellular Adhesion Molecule-1 immunology, Mice, Mice, Inbred BALB C, T-Lymphocytes, Regulatory metabolism, Antibodies, Monoclonal therapeutic use, Cholecalciferol therapeutic use, Graft Rejection therapy, Heart Transplantation, Mice, Inbred C57BL, Postoperative Complications therapy, T-Lymphocytes, Regulatory immunology
- Abstract
Background: Accelerated transplant rejection mediated by donor reactive memory T cells is another barrier to the induction of graft tolerance. The aim of this study was to investigate the immunosuppressing effects of vitamin D (1,25(OH)2D3), administered alone or in combination with a costimulatory blockade treatment, on rejection of secondary heart allografts in a mouse model., Methods: Circular full-thickness skin grafts from BALB/c mice were cut and grafted onto the lumbar regions of C57BL/6 mice as allo-primed recipients. Four weeks after skin grafting, the vascularized hearts from the BALB/c mice were transplanted heterotopically into the allo-primed recipients using a non-suture cuff technique. The recipients were then randomly divided into four groups and given either intraperitoneal injection of isotype, Ab, 1,25(OH)2D3, or a combination of Ab and 1,25(OH)2D3. Allograft incidence was determined by hematoxylin-eosin staining, and cytokine expression was assessed by the quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and cytometric bead arrays. Spleen cells from the recipient were used to assess mixed lymphocyte reactions. Memory T cells and regulatory T cells (Tregs) in spleen cells were measured by flow cytometry., Results: The median allograft survival time was longer with the combined treatment with Ab and 1,25(OH)2D3 than with no treatment or with treatment with Ab or 1,25(OH)2D3 alone. The grafts were protected from infiltration by inflammatory cells and by inhibition of interleukin 2 and interferon gamma expression. Rejection was initially suppressed in the early postoperative period by a reduction in the number of memory T cells and induction of Foxp3
+ Tregs, but this effect disappeared by day 15 after transplantation upon withdrawal of the treatment., Conclusion: Vitamin D3 administered as an immunosuppressive agent, when combined with monoclonal antibody treatment, may protect heart grafts from memory T cell responses in a secondary heart transplant model., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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