HDL and ApoA-I inhibit antigen presentation-mediated T cell activation by disrupting lipid rafts in antigen presenting cells
2012
Wang, Shuhui | Yuan, Shu-guang | Peng, Dao-quan | Zhao, Shui-ping
OBJECTIVE: Depletion of cholesterol by methyl-β-cyclodextrin (MCD) on peptide-loaded antigen presenting cells (APCs) inhibits antigen presentation and T cell activation. However, whether membrane cholesterol efflux induced by high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) also results in inhibition of antigen presentation and T cell activation is still unknown. METHODS AND RESULTS: Various types of APCs, including B cells, macrophages and dendritic cells (DCs), were first loaded with antigen, then incubated with HDL and apoA-I to decrease cellular membrane cholesterol content. After being treated with HDL and apoA-I, APCs demonstrated decreased potential to activate T cells, and this decrease correlated with an increase in cholesterol efflux from APCs. Cholesterol repletion reversed the inhibitory effects of HDL and apoA-I, demonstrating that the observed reduction in T cell proliferation is mediated through cholesterol. Furthermore, lipid raft analysis showed that HDL and apoA-I reduced cholesterol and major histocompatibility (MHC) class II protein content in lipid rafts, suggesting that cholesterol efflux from APCs to HDL and apoA-I inhibits antigen presentation and T cell activation by reducing lipid rafts assembly in APCs. CONCLUSION: HDL and apoA-I inhibit the capacity of APCs to stimulate T cell activation, and this inhibition can be attributed to cholesterol efflux and the ensuing disruption of plasma membrane lipid rafts in APCs. Overall, these findings suggest that cholesterol efflux mediated by HDL and apoA-I may serve to link immunity and cardioprotection.
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