Published online before print February 2, 2006, doi: 10.1161/01.ATV.0000206122.61591.ff
© 2006 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Adoptive Transfer of CD4+ T Cells Reactive to Modified Low-Density Lipoprotein Aggravates Atherosclerosis
From the Center for Molecular Medicine and Department of Medicine, Karolinska Institutet, Stockholm, Sweden. A.-K.L.R.’s current address: Section of Immunobiology, Yale University School of Medicine, New Haven, Conn.
Correspondence to Xinghua Zhou, MD, PhD, FESC, Center for Molecular Medicine L8:03, Karolinska Hospital, SE-17176 Stockholm, Sweden. E-mail Xinghua.Zhou{at}ki.se
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-
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.
To test whether atherogenesis depends on specific disease-associated antigens, we transferred CD4+ T-cells from immunized donors into apoE–/– scid/scid mice. Mice receiving T cells from oxLDL-immunized mice had accelerated lesion progression compared with those receiving naive or KLH-primed T cells. These findings demonstrate that T-cell response to oxLDL is critical in atherogenesis.
Key Words: atherosclerosis • lymphocytes • low-density lipoprotein • immune system • mice, knockout–/–
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