TAP1-Deficiency Does Not Alter Atherosclerosis Development in Apoe (−/−) Mice

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.