Allogenicity of Human Cardiac Stem/Progenitor Cells Orchestrated By Programmed Death Ligand 1
Rationale:Transplantation of allogeneic cardiac stem/progenitor cells (CPC) in experimental myocardial infarction promoted cardiac regeneration and improved heart function. While this has enhanced prospects of using allogeneic CPC for cardiac repair, the mechanisms regulating the behavior of these allogeneic cells, which are central to clinical applications, remain poorly understood.
Objective: T cells orchestrate the allogeneic adaptive immune response. Therefore, to provide insight into the mechanisms regulating the immunologic behavior of human CPC (hCPC), we investigated the allogeneic T-cell response elicited by cryopreserved c-kit-selected hCPC.
Methods and Results: By using an experimental model of allogeneic stimulation, we demonstrate that, whether under inflammatory conditions or not, hCPC do not trigger conventional allogeneic Th1 or Th2 type responses but instead induce proliferation and selective expansion of suppressive CD25highCD127lowHLA-DR+FoxP3high effector regulatory T cells (Treg). The Treg proliferation and amplification was dependent on the interaction with the B7 family member programmed death-ligand 1 (PD-L1) which is substantially expressed on hCPC and increased under inflammatory conditions. Thus, hCPC in allogeneic settings acquire the capacity to down-regulate an ongoing immune response, which was dependent on PD-L1.
Conclusions: Collectively these data reveal that hCPC in allogeneic settings have a “tolerogenic” immune behavior, promoting a contact-PD-L1-dependent regulatory response and a PD-L1-dependent allogeneic-driven immunomodulation. Our study attributes an important role for PD-L1 in the immune behavior of allogeneic hCPC and raises the possibility of using PD-L1 expression as a marker to identify and select low-risk high-benefit allogeneic cardiac repair cells.
- Cardiac progenitor cells
- Cell transplantation
- Myocardial infarction
- T lymphocytes
- Received June 27, 2012.
- Accepted December 12, 2012.
- Copyright © 2012, American Heart Association