Antigen presenting cells (APC) have the ability to present both extra-cellular and intra-cellular antigens via MHC class I molecules to CD8⁺ T cells. The cross presentation of extra-cellular antigens is reduced in mice with deficient Antigen Peptide Transporter 1 (TAP1)-dependent MHC class I antigen presentation, and these mice are characterized by a diminished CD8⁺ T cell population. We have recently reported an increased activation of CD8⁺ T cells in hypercholesterolemic Apoe^−/− mice. Therefore, this study included TAP1-deficient Apoe^−/− mice (Apoe^−/−Tap1^−/−) to test the atherogenicity of CD8⁺ T cells and TAP1-dependent cross presentation in a hypercholesterolemic environment. As expected the CD8⁺ T cell numbers were low in Apoe^−/−Tap1^−/− mice in comparison to Apoe^−/− mice, constituting ∼1% of the lymphocyte population. In spite of this there were no differences in the extent of atherosclerosis as assessed by en face Oil Red O staining of the aorta and cross-sections of the aortic root between Apoe^−/−Tap1^−/− and Apoe^−/− mice. Moreover, no differences were detected in lesion infiltration of macrophages or CD3⁺ T cells in Apoe^−/−Tap1^−/− compared to Apoe^−/− mice. The CD3⁺CD4⁺ T cell fraction was increased in Apoe^−/−Tap1^−/− mice, suggesting a compensation for the decreased CD8⁺ T cell population. Interestingly, the fraction of CD8⁺ effector memory T cells was increased but this appeared to have little impact on the atherosclerosis development.

In conclusion, Apoe^−/−Tap1^−/− mice develop atherosclerosis equal to Apoe^−/− mice, indicating a minor role for CD8⁺ T cells and TAP1-dependent antigen presentation in the disease process.