TAP1-deficiency does not alter atherosclerosis development in Apoe-/- mice.

Area of Science:

• Immunology
• Cardiovascular Research
• Molecular Biology

Background:

• Antigen presenting cells (APCs) present antigens via MHC class I to CD8(+) T cells.
• Antigen Peptide Transporter 1 (TAP1) deficiency impairs cross-presentation and reduces CD8(+) T cells.
• Hypercholesterolemia in Apoe(-/-) mice is associated with increased CD8(+) T cell activation.

Purpose of the Study:

• To investigate the role of CD8(+) T cells and TAP1-dependent antigen presentation in atherosclerosis within a hypercholesterolemic environment.
• To assess the atherogenicity of CD8(+) T cells in Apoe(-/-)Tap1(-/-) mice.

Main Methods:

• Utilized Apoe(-/-)Tap1(-/-) mice, a model combining hypercholesterolemia and TAP1 deficiency.
• Quantified CD8(+) T cell populations and assessed atherosclerosis extent using Oil Red O staining.
• Analyzed immune cell infiltration in aortic lesions, including macrophages and T cell subsets.

Main Results:

• Apoe(-/-)Tap1(-/-) mice exhibited significantly reduced CD8(+) T cell numbers (~1% of lymphocytes) compared to Apoe(-/-) mice.
• No significant differences in atherosclerosis severity were observed between Apoe(-/-)Tap1(-/-) and Apoe(-/-) mice.
• Increased CD3(+)CD4(+) T cell fraction and CD8(+) effector memory T cells were noted in Apoe(-/-)Tap1(-/-) mice, with minimal impact on disease progression.

Conclusions:

• TAP1-dependent antigen presentation and CD8(+) T cells play a minor role in the development of atherosclerosis in this hypercholesterolemic model.
• Apoe(-/-)Tap1(-/-) mice develop atherosclerosis comparable to Apoe(-/-) mice, despite altered T cell populations.