Table 1.

Overview of in vivo experiments determining the role of CTLA4, PD1 and PDL1/2 in atherosclerosis

Study	Model	Atherosclerosis	Effect on plaque	Effect on immune cells
Bu et al49	Pd1−/− Ldlr−/− mice	↑	↑ Lesion size ↑ CD4+ T cells ↑ CD8+ T cells ↑ Macrophages ↑ Apoptotic cells	↑ IFN-γ and TNF-α in splenic T cells
Bu et al49	Antibody-mediated PD1 inhibition in Ldlr−/− mice	↑	=Lesion size ↑ CD4+ T cells ↑ CD8+ T cells	↑ IFN-producing splenic T cells ↑ Lymph node size ↑ Lymph node CD4+ CD8+ T cells
Ewing et al51	Abatacept in femoral arterial cuff ApoE3* Leiden mice	↓	↓ Intimal thickening ↓ Lumenostenosis ↓ Intimal leukocytes	↓ Systemic CD4+ T-cell activation ↓ Splenic regulatory T cells ↓ Plasma IFN-γ
Ewing et al51	Anti-CTLA4 antibody in femoral arterial cuff ApoE3* Leiden mice	↑	↑ Intimal thickening ↑ Lumenostenosis =intimal leukocytes	n/a
Gotsman et al48	Pdl1/2−/− Ldlr−/− mice	↑	↑ Lesion size ↑ CD4+ T cells ↑ CD8+ T cells ↑ Macrophages	↑ Total cells in spleen and lymph node ↑ CD4+ proliferation
Matsumoto et al52	T cell-specific constitutive CTLA4 expression Apoe−/− mice	↓	↓ Lesion size ↓ CD4+ T cells ↓ Macrophages	↓ Splenic CD4+ proliferation
Poels et al53	Anti-CTLA4 antibody in Ldlr−/− mice	↑	↑ Lesion size ↑ Advanced lesions ↑ Necrotic core ↑ CD3+ T cells	↓ Naïve T cells in spleen and circulation ↑ Effector memory T cells in spleen and circulation
Poels et al36	Combined anti-CTLA4 and anti-PD1 antibodies in Ldlr−/− mice	↑	↑ Advanced lesions ↑ Necrotic core ↑ Apoptotic macrophages ↑ CD3+ T cells ↑ CD8+ T cells	↓ Naïve T cells in spleen and circulation ↑ Effector memory T cells in spleen and circulation ↑ Splenic regulatory T cells

↑ indicates an increase in atherosclerotic burden; ↓ indicates a decrease in atherosclerotic burden.

CTLA4, cytotoxic T lymphocyte-associated protein 4; IFN-γ, interferon gamma; PD1, programmed cell death protein 1; PDL1, programmed cell death protein ligand 1.