title: PD-1 and Tim-3 Pathways Regulate CD8+ T Cells Function in Atherosclerosis.
abstract: T cell-mediated immunity plays a significant role in the development of atherosclerosis (AS). There is increasing evidence that CD8+ T cells are also involved in AS but their exact roles remain unclear. The inhibitory receptors programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) are well known inhibitory molecules that play a crucial role in regulating CD8+ T cell activation or tolerance. Here, we demonstrate that the co-expression of PD-1 and Tim-3 on CD8+ T cells is up-regulated in AS patients. PD-1+ Tim-3+ CD8+ T cells are enriched for within the central T (TCM) cell subset, with high proliferative activity and CD127 expression. Co-expression of PD-1 and Tim-3 on CD8+ T cells is associated with increased anti-atherogenic cytokine production as well as decreased pro-atherogenic cytokine production. Blockade of PD-1 and Tim-3 results in a decrease of anti-atherogenic cytokine production by PD-1+ Tim-3+ CD8+ T cells and in an augmentation of TNF-α and IFN-γ production. These findings highlight the important role of the PD-1 and Tim-3 pathways in regulating CD8+ T cells function in human AS.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China.
authors.forename: Ming-Ke
authors.initials: MK
authors.lastname: Qiu
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Song-Cun
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Dai
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China.
authors.forename: Jing-Min
authors.initials: JM
authors.lastname: Ou
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Quan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology*; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor