Induction of dendritic cell-mediated activation of T cells from atherosclerotic plaques by human Heat Shock protein 60

Background--atherosclerosis is characterized by the presence of activated immune-competent cells including dendritic cells (dcs) 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 dcs differentiated from peripheral blood monocytes were treated with human hsp60 or hsp90 and autologous t cells were cocultured with these pretreated dcs (mdcs). hsp60 induced mdcs and t-cell activation as determined by facscan (fluorescence associated cell scan),gene-activation,and cytokine production. hsp60-induced t-cell activation was partly major histocompatibility complex class ii-dependent. t cells exposed to hsp60-treated mdcs produced interferon-γ,interleukin-17,but not transforming growth factor-β. hsp60 did not promote expression of toll-like receptors 2 or 4. hsp90 promoted mdcs maturation but had no effect on t-cell activation. annexin a5 inhibited hsp60-proinflammatory th1/th17 effects on mdcs and t cells,and partly bound hsp60. further,annexin a5 inhibited hsp-induced activation of mdcs and also oxidized low-density lipoprotein-induced hsp-production from mdcs. experiments on mdcs and t cells derived from carotid atherosclerotic plaques from patients with symptomatic carotid disease gave similar results as from blood donors. conclusions--hsp60 induces mdcs activation and partly major histocompatibility complex class ii-dependent activation of bloodand plaque-derived t cells,which is mostly of th1/th17 type. hsp60 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 hsp60,and hsp60- mediated immune activation,which suggests a potential therapeutic role. © 2017 the authors.