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

Adoptive Transfer of CD4 T Cells Reactive to Modified Low-Density Lipoprotein Aggravates Atherosclerosis,Xinghua Zhou,Anna-Karin L. Robertson,Charlott

Adoptive Transfer of CD4 T Cells Reactive to Modified Low-Density Lipoprotein Aggravates Atherosclerosis   (Citations: 17)
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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 naõ ¨ve 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- 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. (Arterioscler Thromb Vasc Biol. 2006;26:864-870.)
Published in 2011.
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