PD-1 and Tim-3 Pathways Regulate CD8+ T Cells Function in Atherosclerosis: e0128523

• Published in: PloS one Vol. 10; no. 6
• Main Authors: Qiu, Ming-Ke, Wang, Song-Cun, Dai, Yu-Xin, Wang, Shu-Qing, Ou, Jing-Min, Quan, Zhi-Wei
• Format: Journal Article
• Language: English
• Published: 01.06.2015
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0128523

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- alpha and IFN- gamma production. These findings highlight the important role of the PD-1 and Tim-3 pathways in regulating CD8+ T cells function in human AS.