Lack of Ability to Present Antigens on MHC Class II Molecules Aggravates Atherosclerosis in ApoE-/- Mice

Background: Hypercholesterolemic mice lacking factors required for activation of CD4+ T cells are characterized by reduced development of atherosclerosis. Consequently, it has been assumed that atherosclerosis involves loss of tolerance against modified self-antigens generated in response to hypercholesterolemia and that presentation of such antigens on MHC class II lead to activation of pro-atherogenic Th1 cells. In this study, we wanted to determine the role of antigen presentation on MHC class II in atherosclerosis development. Methods: ApoE-/- mice deficient for MHC class II (ApoE-/-MHCII-/-) were used to study the role of MHCII in atherosclerosis development. Results: In comparison to ApoE-/- mice, ApoE-/-MHCII-/-mice had reduced levels of CD4+ T cells, IgG and IgM levels, as well as reduced Th1 and Th2 cytokines in plasma. CD8+ T cells were increased and regulatory T cells were reduced both in spleen and in lesions of ApoE-/-MHCII-/- mice. Decreased plasma levels of inflammatory cytokines in ApoE-/-...