Abstract:

BACKGROUND: A body of evidences support that CD4⁺CD25⁺Foxp3⁺ regulatory T cells is associated with oral tolerance induction and inhibition of atherosclerosis, but little is described whether nasal tolerance to antigen likewise induce the regulatory T cell production and antiatherosclerotic benefit.
OBJECTIVE: To investigate the effect of nasal tolerance induction to heat shock protein-65 (HSP65) on atherogenesis and potential mechanism.
METHODS: Six-week-old male ApoE-/- mice were nasally administrated HSP65 or phosphate buffer as control. Cryo-section was used to examine the size of atheromatous plaque area of aortic root in ApoE-/- mice with sixteen-week-old; fluorescence activated cell sorter was used to analyse the production level of CD4⁺CD25⁺Foxp3⁺ regulatory T cells; ELISA was applied to determine the level of cytokines transforming growth factor beta (TGF-β).
RESULTS AND CONCLUSION: Eight weeks after nasal administration, the results of cryo-section showed that HSP65-treated mice had a marked decrease by 32.7% in atheromatous plaque area of aortic root as compared with the control group (P < 0.01). At 14 days after the last nasal treatment, the percentage of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in total CD4⁺ T cells from treated mice increased significantly as compared with the control group (P < 0.01), at 4,14 days and 8 weeks after the last nasal administration, cytokine TGF-β level from nasal HSP65 mice increased remarkably compared with the control group on the above three points. So, nasal tolerance induction to heat shock protein-65 inhibits atherosclerotic formation by inducing anti-inflammatory cytokine TGF-β-dependent regulatory T cells. It is proposed that nasal tolerance induction to HSP65 may provide an alternative therapeutic method to atherosclerosis.