251. Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein aggravates atherosclerosis.
- Author
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Zhou X, Robertson AK, Hjerpe C, and Hansson GK
- Subjects
- Adjuvants, Immunologic, Adoptive Transfer, Animals, Apolipoproteins E deficiency, Apolipoproteins E genetics, Atherosclerosis blood, Atherosclerosis pathology, Autoantigens immunology, CD4-Positive T-Lymphocytes pathology, CD4-Positive T-Lymphocytes transplantation, Hemocyanins immunology, Immunity, Cellular, Interferon-gamma blood, Interleukin-5 blood, Interleukins blood, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Th1 Cells immunology, Th1 Cells pathology, Atherosclerosis immunology, CD4-Positive T-Lymphocytes immunology, Lipoproteins, LDL immunology
- 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-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.
- Published
- 2006
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