Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein aggravates atherosclerosis
| Autor: | Xinghua Zhou, Göran K. Hansson, Charlotta Hjerpe, Anna-Karin L. Robertson |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Apolipoprotein E
CD4-Positive T-Lymphocytes Adoptive cell transfer Mice SCID Autoantigens chemistry.chemical_compound Interferon-gamma Mice Immune system Apolipoproteins E Antigen Adjuvants Immunologic Animals Mice Knockout Immunity Cellular biology Interleukins T lymphocyte Th1 Cells Atherosclerosis Adoptive Transfer Lipoproteins LDL Mice Inbred C57BL chemistry Low-density lipoprotein Immunology Hemocyanins biology.protein Interleukin-5 Cardiology and Cardiovascular Medicine Keyhole limpet hemocyanin Lipoprotein |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 26(4) |
| ISSN: | 1524-4636 |
| Popis: | 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/scidmice 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/scidmice. 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/scidcontrols. 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. |
| Databáze: | OpenAIRE |
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