Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein aggravates atherosclerosis.
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.


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-gamma were increased in proportion to the acceleration of atherosclerosis.


CONCLUSIONS
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.
Zhou
Xinghua
X
Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Xinghua.Zhou@ki.se
Robertson
Anna-Karin L
AK
Hjerpe
Charlotta
C
Hansson
Göran K
GK
D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D006433:Hemocyanins / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D007378:Interleukins / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
D000276:Adjuvants, Immunologic; D001057:Apolipoproteins E; D001324:Autoantigens; D015848:Interleukin-5; D007378:Interleukins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin