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

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 26; no. 4; pp. 864 - 870
• Main Authors: Zhou, Xinghua, Robertson, Anna-Karin L, Hjerpe, Charlotta, Hansson, Göran K
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.04.2006; Hagerstown, MD Lippincott
• Subjects: Adjuvants, Immunologic; Adoptive Transfer; Animals; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Atherosclerosis (general aspects, experimental research); Atherosclerosis - blood; Atherosclerosis - immunology; Atherosclerosis - pathology; Autoantigens - immunology; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - transplantation; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fundamental and applied biological sciences. Psychology; Hemocyanins - immunology; Immunity, Cellular; Interferon-gamma - blood; Interleukin-5 - blood; Interleukins - blood; Lipoproteins, LDL - immunology; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Pharmacology. Drug treatments; Th1 Cells - immunology; Th1 Cells - pathology; Vertebrates: cardiovascular system; lymphocytes; Rodentia; Cardiovascular disease; Lipoprotein; low-density lipoprotein; Vascular disease; Vertebrata; Mammalia; Mouse; Animal; Atherosclerosis; T-Lymphocyte; mice, knockout-; Immune system
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/01.ATV.0000206122.61591.ff

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.