Recovery of endothelial dysfunction with tolerogenic dendritic cell loaded with heat shock protein 60 in apolipoprotein E-null mice

AIM: To examine whether tolerogenic dendritic cells (DC) loaded with heat shock protein 60 (HSP60) could restore endothelial function in hypercholesterolemic apolipoprotein E (apoE)-null mice.METHODS: Bone marrow derived DC of the mice was loaded with HSP60 and co-cultured with rapamycin to generate tolerogenic DC.The tolerogenic DC, DC loaded only with HSP60 (DChsp) and saline were injected into the apoE-null mice at 6 weeks of age for two times at a one-week interval.C57BL/6 mice at the same age were taken as normal control two weeks after the last injection.Aorta was harvested for ex vivo vascular ring tension test.Immune parameters were also analyzed in vitro and in vivo.RESULTS: Compared with the non loaded DC, HSP60 pulsed DC expressed higher levels of CD86, and stimulated T lymphocytes to proliferation significantly, while the tolerogenic DC expressed lower levels of CD86, and inhibited T lymphocytes to proliferation.After immunization with different injection, Ach-induced relaxation was reduced significantly in DChsp group compared with saline group (P<0.01).Treatment of mice with tolerogenic DC restored endothelium-dependent dilation in a dose-dependent manner (P<0.01).The improvement in endothelial function was associated with a reduction in T cell response to HSP60.CONCLUSION: Our results indicate a rapid improvement in endothelial function with HSP60 tolerogenic DC immunization, and suggest that this immune therapy has significant vasculoprotective effects.