Open AccessInduction of Dendritic Cell–Mediated Activation of T Cells From Atherosclerotic Plaques by Human Heat Shock Protein 60
Author(s) -
Rahman Mizanur,
Steuer Johnny,
Gillgren Peter,
Hayderi Assim,
Liu Anquan,
Frostegård Johan
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.006778
Subject(s) - t cell , heat shock protein , proinflammatory cytokine , medicine , annexin a5 , antigen presenting cell , cd40 , immune system , immunology , cytokine , microbiology and biotechnology , annexin , inflammation , cytotoxic t cell , biology , flow cytometry , in vitro , biochemistry , gene
Background Atherosclerosis is characterized by the presence of activated immune‐competent cells including dendritic cells ( DC s) and T cells, dead cells, and oxidized low‐density lipoprotein. HSP60 (Heat shock protein 60) has been implicated in atherosclerosis. A plasma protein, Annexin A5, has atheroprotective properties. Methods and Results Human DC s differentiated from peripheral blood monocytes were treated with human HSP 60 or HSP 90 and autologous T cells were cocultured with these pretreated DC s ( mDC s). HSP 60 induced mDC s and T‐cell activation as determined by FACS can (Fluorescence associated cell scan), gene‐activation, and cytokine production. HSP 60‐induced T‐cell activation was partly major histocompatibility complex class II –dependent. T cells exposed to HSP 60‐treated mDC s produced interferon‐γ, interleukin‐17, but not transforming growth factor‐β. HSP 60 did not promote expression of Toll‐like receptors 2 or 4. HSP 90 promoted mDC s maturation but had no effect on T‐cell activation. Annexin A5 inhibited HSP 60‐proinflammatory Th1/Th17 effects on mDC s and T cells, and partly bound HSP 60. Further, Annexin A5 inhibited HSP ‐induced activation of mDC s and also oxidized low‐density lipoprotein–induced HSP ‐production from mDC s. Experiments on mDC s and T cells derived from carotid atherosclerotic plaques from patients with symptomatic carotid disease gave similar results as from blood donors. Conclusions HSP 60 induces mDC s activation and partly major histocompatibility complex class II –dependent activation of blood‐ and plaque‐derived T cells, which is mostly of Th1/Th17 type. HSP 60 could thus be an important T‐cell antigen in plaques, and also mediate oxidized low‐density lipoproteins immunogenic effects on DC ‐T‐cell activation, promoting plaque rupture and clinical manifestations of cardiovascular disease. Annexin A5 inhibits both oxidized low‐density lipoprotein–induced HSP 60, and HSP 60‐mediated immune activation, which suggests a potential therapeutic role.