Activation Inventor Professional 2019 Activation
Activation Inventor Professional 2019 Activation
strikingly, the cytokine production by t cells from human plaques is much stronger than that induced by t cells from peripheral blood. this pattern was observed for both oxldl-induced and pc-induced t-cell activation. to our knowledge, this is the first time that human plaque-derived t cells have been shown to be as potent as the same cells from peripheral blood in responding to immunomodulators. our data demonstrate that atherosclerotic plaque t cells are readily available for immune activation in situ and that the oxidation of ldl is one stimulus that potentially can be used to activate these cells.
in this study, using the same pathway, we examined the effects of mda-hsa-induced dc-mediated t-cell activation in atherosclerosis. after treatment of dendritic cells with mda-hsa, we found that t cells from plaques and blood could be induced to proliferate and produce ifn- in vitro and a pro-inflammatory profile of cytokines was demonstrated in these t cells. direct t-cell activation induced by mda-hsa was also demonstrated. atherosclerotic mda-modified hsa peptides were identified by mass spectrometry in atherosclerotic patients’ hsa. mda-modified hsa induced activation of t cells, which could be blocked by an inhibitor of oxidative stress and antibodies against mda-hsa. these findings demonstrate that mda-hsa can affect the immune system by direct t-cell activation and dc-mediated activation of t cells in atherosclerosis.
our experiments demonstrate that atherosclerotic plaque induces local activation of t cells. we postulate that mda-hsa may induce activation of t cells in atherosclerosis by binding to the tcr. mda modification of protein may mediate t-cell activation and induce cytokine production. a relatively small amount of mda-hsa is sufficient to mediate dc-t-cell activation in atherosclerosis. the presence of atherosclerotic plaque-derived mda-modified hsa in atherosclerotic plaques may lead to local activation of t cells, which play an important role in atherogenesis. therefore, mda-hsa is potentially a novel biomarker of atherosclerosis.
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