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Endothelial Stromal PD-L1 (Programmed Death Ligand 1) Modulates CD8+ T-Cell Infiltration After Heart Transplantation
William Bracamonte-Baran1,2, Nisha A Gilotra3, Taejoon Won1
1Department of Pathology, School of Medicine (W.B.-B., T.W., M.V.T., R.A.A., Q.Z., M.K.H., D.Č.), Johns Hopkins University, Baltimore, MD.
Circulation. Heart Failure
|September 24, 2021
Summary
Loss of PD-L1 expression in heart transplant grafts may increase CD8+ T cell infiltration and rejection. This highlights the PD1/PD-L1 axis's role in cardiac immune homeostasis and transplant outcomes.
Area of Science:
- Immunology
- Transplantation Science
- Cardiology
Background:
- The role of checkpoint inhibitors, specifically the PD1/PD-L1 axis, in human transplantation is not well understood.
- Fulminant myocarditis with allorejection-like features in patients on anti-PD1 therapy suggests a critical role in cardiac immune regulation.
Purpose of the Study:
- To investigate the role of the PD1/PD-L1 axis in human heart transplant immune homeostasis.
- To correlate PD-L1 expression in graft tissues with immune cell infiltration and rejection markers.
Main Methods:
- Cross-sectional study of 23 heart transplant patients undergoing surveillance endomyocardial biopsy.
- Flow cytometry analysis of endomyocardial tissue and peripheral blood mononuclear cells.
- Multivariate logistic regression and murine models to assess PD-L1's impact on allorejection.
Main Results:
- Myeloid cells predominated in the graft leukocyte compartment; CD4:CD8 T-cell ratios varied.
- PD-L1 expression on graft endothelial cells, fibroblasts, and myeloid leukocytes ranged up to 60%.
- A significant inverse correlation was found between PD-L1+ HLA-DR+ endothelial cells and CD8+ T cells (P=0.030).
- Murine models showed faster rejection of grafts lacking endothelial PD-L1.
Conclusions:
- Loss of graft endothelial PD-L1 may regulate CD8+ T-cell infiltration in human heart transplantation.
- Endothelial PD-L1 expression appears crucial for preventing accelerated allograft rejection.
