Adoptive Transfer of CD4 + T Cells Reactive to Modified Low-Density Lipoprotein Aggravates Atherosclerosis

Abstract

Objective— Atherosclerosis is associated with immune responses to oxidized low-density lipoprotein (oxLDL). The presence of activated macrophages and T cells in lesions suggests that cell-mediated immune reactions are taking place during the disease process. However, the role of specific immune responses has remained unclear. We have previously shown that transfer of CD4 + T cells from apolipoprotein E knockout mice (apoE −/− ) into immunodeficient apoE −/− scid/scid mice accelerates disease. Methods and Results— To test whether this effect is dependent on specific disease-associated antigens, purified CD4 + T cells from oxLDL-immunized mice were transferred into apoE −/− scid/scid mice. CD4 + T cells from mice immunized with a nonrelevant antigen, keyhole limpet hemocyanin (KLH), and naïve CD4 + T cells were used as controls. After 12 weeks, all mice that received T cells had larger lesions than untouched apoE −/− scid/scid controls. However, mice receiving CD4 + T cells from oxLDL immunized mice had substantially accelerated lesion progression compared with those receiving naive or KLH-primed T cells. Circulating levels of interferon-γ were increased in proportion to the acceleration of atherosclerosis. Conclusion— These data show that adoptive transfer of purified CD4+ T cells from oxLDL-immunized mice accelerates atherosclerosis. They support the notion that Th1 cellular immunity is proatherogenic and identify oxLDL as a culprit autoantigen.