Key result
PD-L1 deletion or blockade transforms transient myocarditis into lethal disease driven by leukocyte-rich microabscesses.
Why the study?
The role of PD-L1 expressed on cardiac endothelial cells in regulating immune-mediated injury in the heart was not well understood.
Does PD-L1 signaling regulate immune-mediated cardiac injury in mice with cytotoxic T-lymphocyte-induced myocarditis?
Population
Mice with cytotoxic T-lymphocyte-mediated myocarditis including PD-L1/L2-deficient and wild-type mice
Comparison
PD-L1/2 genetic deletion and PD-L1 blocking antibody vs wild-type or untreated controls
Design
Preclinical experimental study in mice
Authors
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PD-L1 blockade may convert transient myocarditis to lethal disease in this model; leaves open relevance to human checkpoint inhibitor cardiotoxicity.
Does PD-L1 signaling regulate immune-mediated cardiac injury in mice with cytotoxic T-lymphocyte-induced myocarditis?
Myocardial PD-L1, primarily on the endothelium, plays a critical protective role against immune-mediated cardiac injury and lethal myocarditis.
Grabie et al. (2007) studied Cytotoxic T-lymphocyte-mediated myocarditis. PD-L1/L2 deficiency or PD-L1 blocking antibody vs. Wild-type mice / no blocking antibody was evaluated on Disease severity and lethality. Genetic deletion of PD-1 ligands or treatment with PD-L1 blocking antibody transformed transient myocarditis into a lethal disease with widespread polymorphonuclear leukocyte-rich microabscesses.
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