PD-L1/2 deficiency led to:• increased systemic CD4+ and CD8+ T-cell activation• expansion of both pro-atherogenic IFNγ-secreting TH1 and atheroprotective Foxp3+ Tregs• massive infiltration of T cells in atherosclerotic lesions• aggravated hypercholesterolemia and exacerbated atherosclerotic lesion development. Here, CD8A is linked to familial hypercholesterolemia.