FK506作为佐剂刺激Tfh细胞增强体液免疫水平的研究

目的:探讨他克莫司(FK506)作为佐剂通过刺激Tfh细胞增强疫苗体液免疫水平的机制。方法:利用FK506与模式蛋白(卵清白蛋白,OVA)皮下注射免疫BALB/c小鼠,免疫三次,利用ELISA方法检测抗体水平;利用抗体染色流式细胞仪检测Tfh细胞、B细胞表面分子IL-21R及记忆性B细胞标志分子CD27表达。结果:FK506作为OVA蛋白佐剂,能够显著提高小鼠OVA特异性的IgG水平,增强体液免疫水平;免疫后的小鼠Tfh细胞表达IL-21水平显著高于其他对照组。同时,B细胞表达IL-21R及记忆性B细胞标志分子CD27显著高于其他对照组。表明FK506作为佐剂刺激Tfh细胞表达IL-21,作用于B细胞增强抗体水平。结论:FK506能够作为蛋白疫苗佐剂刺激Tfh细胞表达IL-21;IL-21可能通过与B细胞表面IL-21R作用,增强抗体的分泌;并刺激记忆性B细胞的产生,进而增强体液免疫水平。

Stimulation of Tfh cells and enhancement humoral immune responses with FK506 as adjuvant

Objective: To study the mechanism of stimulation of Tfh cells and enhancement of humoral immune responses by FK506 as adjuvant of vaccines.Methods: BALB / c mice were injected subcutaneously with tacrolimus(FK506) combined with OVA protein three times.The serum were collected and the antibody titer were checked by ELISA;the Tfh cells and the surface molecule IL21R and memory marker molecule CD27 of B cells were stained with monoclonal antibodies and analyzed by FACS.Results: The OVA specific IgG level of immunized mice was increased significantly which indicated the humoral immunity was improved.And IL-21 expression of Tfh cells were increased of mice immunized with FK506 / OVA compared with other groups.Furthermore,the expression level of IL-21R and CD27 on B cell were increased of mice immunized with FK506 / OVA compared with other groups,which demonstrated that FK506 as an adjuvant of OVA can stimulate Tfh cells to secrete more IL-21 that activated B cell to produce high level antibodies.Conclusion: The results firstly demonstrated that FK506 as an adjuvant of protein vaccine can stimulate the expression of IL-21 in Tfh cells;and the IL-21 can interact with IL-21R expressed on B cells surface for enhancement of antibodies secretion;even more memory B cells were induced and humoral immune response enhanced.