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Kidney Week

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.