@article {542611, title = {B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice.}, journal = {Circulation}, volume = {109}, number = {16}, year = {2004}, month = {2004 Apr 27}, pages = {2009-15}, abstract = {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.}, keywords = {Animals, Antigens, Antigens, CD, Antigens, CD80, Antigens, CD86, Arteriosclerosis, CD4-Positive T-Lymphocytes, Chaperonin 60, Cholesterol, Cytokines, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Knockout, Receptors, LDL}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000127121.16815.F1}, author = {Buono, Chiara and Pang, Hong and Uchida, Yasushi and Libby, Peter and Sharpe, Arlene H and Lichtman, Andrew H} }