Abstract: FR-PO1122
Human Donor-Specific Regulatory T-Cell Line Function Is Mediated Through the Adenosinergic Pathway
Session Information
- Transplantation: Basic
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1901 Transplantation: Basic
Authors
- Martin Moreno, Paloma L., Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Tripathi, Sudipta, Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Waaga-Gasser, Prof. dr. ana maria, Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Chandraker, Anil K., Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
Background
We have previously shown that regulatory T cell lines generated and expanded from transplanted individuals have the capacity to induce longterm allograft survival in an animal model and suppress human donor specific effector T cell responses in vitro. In murine models targeting the CD39/73 adenosinergic pathway is associated with long-term graft function and reduced graft versus host disease severity. Little is known about the role of this pathway in human regulatory T cells.
Methods
45 Kidney transplant recipients were included in the study and 19 T-cell lines were generated from 17 patients by stimulating PBMCs with mismatched donor-derived HLA-DR allopeptides. T-cell lines were immunophenotyped with fluorphore conjugated human anti-CD39 and anti-CD73 and analyzed using Flowjo. Involvement of the adenosinergic pathway by using Adenosine A2A receptor (A2Ar) antagonist.
Results
The functional characterization of the ex vivo expanded T-cell lines was determined by assessing their immunosuppressive function to inhibit antigen specific and non specific T cell proliferation. We observed that all ex vivo expanded T-cell lines were able to substantially inhibit donor antigen specific T cell proliferation. Expression of both CD39 and CD73 in our T-cell lines, both related to the adenosinergic pathway. Inhibition using the A2Ar antagonist Istradefylline resulted in abrogation of suppression and increase in antigen specific T cell proliferation (Figure).
Conclusion
Our results suggest that the CD39/CD73 adenosinergic pathway is important in the function of regulatory T cells and therapies targeting CD39 and CD73 may enhance human regulatory T cell function.