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

Abstract

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. © 2012 Kolbus et al.