A functional role for inducible costimulator (ICOS) in atherosclerosis

被引:31
作者
Afek, A
Harats, D
Roth, A
Keren, G
George, J
机构
[1] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Cardiol, IL-69978 Tel Aviv, Israel
[2] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Cardiovasc Res Lab, IL-69978 Tel Aviv, Israel
[3] Chaim Sheba Med Ctr, Inst Pathol, IL-52621 Tel Hashomer, Israel
[4] Chaim Sheba Med Ctr, Inst Lipid & Atherosclerosis Res, IL-52621 Tel Hashomer, Israel
关键词
atherosclerosis; immune system; lymphocyte; oxidized LDL;
D O I
10.1016/j.atherosclerosis.2005.03.040
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Lymphocytes appear to influence atherosclerosis by altering cytokine production. Whereas primary lymphocyte activation requires T cell receptor ligation, costimulatory signals also appear requisite for generation of a functional T cell response. Inducible costimulator (ICOS) is a newly discovered T cell molecule with a dual role in immune mediated disorders. Herein, we tested the importance of ICOS in atherosclerosis. Methods and results: Atherosclerotic plaques from ApoE-KO mice were studied immunohistochemically for the presence and localization of ICOS and its receptors and its expression in splenocytes. ApoE-KO mice were immunized with human ICOS/Fc-chimera or non-fused Fc and either provided a chow diet for 6 weeks, or a high fat diet for 8 weeks. ICOS and its ligand were abundantly expressed with in plaques from ApoE- KO in ice: Spleen cells from atherosclerotic mice exhibited lowered constitutive expression of ICOS yet priming with oxLDL enhanced ICOS expression dose-dependently. In mice induced to develop fatty streaks and to generate ICOS blocking antibodies, early atherosclerosis was increased by similar to 77% whereas upon inducing more advanced lesions, the increase in plaque area upon ICOS blockade group was similar to 36%. IFN-gamma secretion by oxLDL-primed splenocytes in ICOS-immunized mice increased whereas IL-10 secretion diminished as compared to control animals. A similar trend in cytokine production was evident in the lesion by immunohistochemistry. Conclusion: ICOS appears as an influential costimulatory, pathway in atherosclerosis that may play a protective rather that a proatherogenic role. (c) 2005 Published by Elsevier Ireland Ltd.
引用
收藏
页码:57 / 63
页数:7
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