B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice

Article

关键词: HEAT-SHOCK PROTEIN-65;    CD40 LIGAND;    ATHEROSCLEROSIS;    LYMPHOCYTES;    AUTOIMMUNE;    GAMMA;    HEAT-SHOCK-PROTEIN-60;    PATHOGENESIS;    INFLAMMATION;    ACTIVATION;   

DOI  :  10.1161/01.CIR.0000127121.16815.F1

来源: SCIE

【 摘 要 】

Background-Several lines of evidence indicate that T-cell responses influence the progression of atherosclerotic disease. Interferon-gamma (IFN-gamma)-producing T cells specific for lesional antigens, including oxidized LDLs and heat shock protein 60 (HSP60), may promote lesion development as well as plaque instability. B7-1 and B7-2 are closely related molecules expressed on antigen-presenting cells that provide costimulatory signals for T-cell activation. This study tested the hypothesis that the ability of T cells to influence atherosclerosis depends on B7-1/B7-2 costimulation. Methods and Results-B7-1/B7-2/LDL receptor (LDLR)-deficient mice and LDLR-deficient control mice were fed a 1.25% cholesterol or control diet for 8 and 20 weeks. Total serum cholesterol levels and extent and phenotype of atherosclerosis were analyzed. Splenic and lymph node CD4(+) T cells from the animals were cultured with mouse recombinant HSP60 or media and antigen-presenting cells and analyzed for IFN-gamma and interleukin-4 production. The absence of B7-1 and B7-2 significantly reduced early cholesterol diet-induced atherosclerotic lesion development in LDLR-deficient mice compared with B7-1/B7-2-expressing control mice. Furthermore, CD4(+) T cells from the cholesterol-fed B7-deficient mice secreted a significantly lower amount of IFN-gamma in response to mouse HSP60 in vitro than did T cells from B7-expressing control mice. Conclusions-The data show that B7-1 and B7-2 regulated the development of atherosclerotic lesions and the priming of lesional antigen-specific T cells. This study highlights the B7-CD28 pathway as a potentially important target for immunomodulation of atherosclerosis.

【 授权许可】

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