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Updated: Jun 30, 2026
An Immunological Model for Heterotopic Heart and Cardiac Muscle Cell Transplantation in Rats
Published on: May 8, 2020
PD-L1/PD-1 signal deficiency promotes allogeneic immune responses and accelerates heart allograft rejection
Weigang Wang1, Katie Carper, Frances Malone
1Division of Transplantation, Department of Surgery, University of Washington Medical Center, Seattle, WA 98195, USA.
Background:
PD-L1, a ligand for programmed death 1 (PD-1), delivers a negative costimulatory signal to T cells and plays a critical role in the regulation of peripheral tolerance.
Methods:
We used PD-L1(-/-) mice to evaluate the role of the PD-L1 signal on allogeneic immune responses in vivo and the underlying mechanisms. Heart transplantation was performed from PD-L1(-/-) donors or recipients in major histocompatibility complex fully mismatched mouse combinations. The immunologic function of allograft recipients was evaluated ex vivo by enzyme-linked immunospot, mixed lymphocytes reaction, cytotoxic T lymphocyte, and flow cytometry.
Results:
Our results demonstrated that PD-L1(-/-) T cells proliferated vigorously under alloantigen stimulation, and also that the antigen-presenting cells (APCs) from PD-L1(-/-) mice exhibited a stronger allostimulatory activity compared with that in wild-type mice. Heart allografts were rejected at an accelerated rate in both PD-L1(-/-) donors and recipients. This was associated with significantly augmented donor specific T-cell proliferation and antidonor cytotoxic T lymphocyte activities, and enhanced Th1- or Th2-type immune responses of heart allograft recipients.
Conclusions:
Absence of PD-L1 input triggers a stimulatory signal to effector T cells and APCs, accelerating heart allograft rejection. Engagement of the PD-L1 signal on T cells or APCs may be necessary to induce transplant tolerance.
