Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses—Brief Report. Issue 9 (September 2016)

• Record Type: Journal Article
• Authors: Meiler, Svenja; Smeets, Esther; Winkels, Holger; Shami, Annelie; Pascutti, Maria Fernanda; Nolte, Martijn A.; Beckers, Linda; Weber, Christian; Gerdes, Norbert; Lutgens, Esther
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 36:Issue 9(2016)
• Publication Date: 2016-09
• Subjects: atherosclerosis -- bone marrow -- effector memory T cells -- GITR ligand -- regulatory T cells; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.116.307354
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective—: Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed on CD4 + effector memory T cells and regulatory T cells; however, its role on these functionally opposing cell types in atherosclerosis is not fully understood. Approach and Results—: Low-density lipoprotein receptor–deficient mice ( Ldlr −/− ) were lethally irradiated and reconstituted with either bone marrow from B-cell–restricted Gitrl transgenic mice or from wild-type controls and fed a high-cholesterol diet for 11 weeks. Chimeric Ldlr −/− Gitrl tg mice showed a profound increase in both CD4 + effector memory T cells and regulatory T cells in secondary lymphoid organs. Additionally, the number of regulatory T cells was significantly enhanced in the thymus and aorta of these mice along with increased Gitrl and Il-2 transcript levels. Atherosclerotic lesions of Ldlr −/− Gitrl tg chimeras contained more total CD3 + T cells as well as Foxp3 + regulatory T cells overall, leading to significantly less severe atherosclerosis. Conclusions—: These data indicate that continuous GITR stimulation through B cell Gitrl acts protective in a mouse model of atherosclerosis by regulating the balance between regulatory and effector memory CD4 + T cells. Abstract : Supplemental Digital Content is available in the text.