Contributions of PD-1/PD-L1 pathway to interactions of myeloid DCs with T cells in atherosclerosis.
Although inflammatory cells contribute to immunopathogenesis of atherosclerosis, underlying molecular mechanisms remain largely undefined. Recently, it has been demonstrated in mouse model that Programmed death-1 (PD-1)/PD-1 ligand (PD-L) pathway plays a critical role in proatherogenic immune responses. Here we examined the expression of PD-1 and PD-L1 on peripheral blood mononuclear cells by flow cytometry in 76 patients with coronary artery disease (CAD), and 25 healthy volunteers. The expression of PD-1 and PD-L1 is significantly down-regulated on T cells and myeloid dendritic cells (mDCs) in CAD patients than in healthy individuals, respectively. More importantly, we found that decreased PD-L1 expression on mDCs is related with the increased T cell immune responses in CAD patients. In addition, stimulation of PD-L1 expression in vitro could attenuate the stimulatory ability on allogeneic T cell proliferation and its cytokine production, including IFN-gamma and IL-2, and also influence the production of IL-10 and IL-12 by mDCs. Taken together, we can draw a conclusion that PD-1/PD-L1 pathway plays a key role in the regulation of proatherogenic T cell immunity by intervening antigen presenting cell (APC)-dependent T cell activation, which associates with pro-inflammatory or anti-inflammatory cytokine production, and further studies need gain insight into that this pathway represents a strategy of immunotherapy for atherosclerosis.
Lee
Jun
J
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Baqiao District, Xi'an 710038, P R China.
Zhuang
Yan
Y
Wei
Xin
X
Shang
Fujun
F
Wang
Jiuping
J
Zhang
Ye
Y
Liu
Xiongtao
X
Yang
Yuhui
Y
Liu
Li
L
Zheng
Qiangsun
Q
D000368:Aged; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism* / Q000502:physiology; D050197:Atherosclerosis / Q000378:metabolism*; D060890:B7-H1 Antigen; D016022:Case-Control Studies; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016898:Interferon-alpha; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor