上海市卡介苗接种人群外周抗原特异性T细胞免疫应答特征谱

Characteristics of peripheral antigen-specific T cell immune response in BCG vaccinated population in Shanghai

为探究抗原特异性T细胞功能动态变化与卡介苗(Bacillus Calmette-Guérin,BCG)保护时效的相关性,采用酶联免疫斑点法(enzyme-linked immunospot assay,ELISPOT)和流式细胞术对上海地区健康志愿者外周抗原特异性CD4^(+)T细胞应答水平进行评估。结果显示,IFN-γ水平随着个体年龄的增长而升高(P<0.05);30岁以上人群分泌抗原特异性IFN-γ的CD4效应T细胞(effector T cell,T_(eff))比例显著升高(P<0.01),同时18岁以上人群分泌IFN-γ的CD4记忆T细胞(memory T cell,T_(M))比例显著下降(P<0.05);成年人IL-17α^(+)CD4^(+)T细胞和CD4^(+)T_(eff)比例均显著高于青少年人群(P<0.01);此外,18~29岁人群外周CD4^(+)初始T细胞(na6ve T cell,T_(N))和CD4^(+)T_(eff)以分泌IL-17α为主,而大于30岁的人群外周分泌IFN-γ的CD4^(+)T_(M)比例下降(P<0.0001),且二者趋向于平衡。上述结果提示,接种BCG后,个体随年龄增长其外周抗原特异性的Th1和Th17 T_(eff)和T_(M)格局发生变化,可能在抗结核分枝杆菌(Mycobacterium tuberculosis,Mtb)感染中发挥一定的保护作用。因此,设计特定的亚单位结核疫苗以加强长效免疫T_(M)的保护性将对结核病的防控具有重要意义。

The study aims to explore the correlation between the dynamic changes in antigen-specific T cell function and the protection duration of Bacillus Calmette-Guérin(BCG)vaccine.Enzyme-linked immunospot assay(ELISPOT)and flow cytometry were used to assess the response level of peripheral antigen-specific CD4~+T cells in healthy volunteers in Shanghai.The results showed that the levels of IFN-γincreased with the age of individual(P<0.05).In population aged 30 and above,the percentage of IFN-γ-secreting antigen-specific CD4~+effector T cells(T_(eff))significantly increased(P<0.01).At the same time,the percentage of IFN-γ-producing CD4~+memory T cells(T_M)in the population aged 18 and above significantly decreased(P<0.05).Both IL-17α~+CD4~+T cells and CD4~+T_(eff)were significantly higher in adults than adolescents(P<0.01).Additionally,in the 18-29 age group,peripheral CD4~+na6ve T cells(T_N)and CD4~+T_(eff)primarily secreted IL-17α,whereas in the population over 30,the percentages of CD4~+T_(M)secreting IFN-γdecreased(P<0.0001),and the two subsets were in balance.These findings suggest that following BCG vaccination,the peripheral antigen-specific Th1,Th17 T_(eff),and T_(M)response profiles change with individual age and may play a protective role against Mycobacterium tuberculosis(Mtb)infection.Therefore,the design of specific tuberculosis subunit vaccines to enhance the protective long-term T_(M)response may be critical for tuberculosis prevention and control.