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,Teff)比例显著升高(P＜0.01),同时18岁以上人群分泌IFN-y的CD4记忆T细胞(memory Tcell,TM)比例显著下降(P＜0.05);成年人IL-17α+CD4+T细胞和CD4+Teff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(naive T cell,TN)和CD4+Teff以分泌IL-17α为主,而大于30岁的人群外周分泌IFN-γ的CD4+TM比例下降(P＜0.000 1),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Thl和Th17 Teff和TM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TM的保护性将对结核病的防控具有重要意义.
Characteristics of peripheral antigen-specific T cell immune response in BCG vaccinated population in Shanghai
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 cytom-etry 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-y increased with the age of individual(P＜0.05).In population aged 30 and above,the percentage of IFN-y-secreting antigen-specific CD4+effector T cells(Teff)significantly increased(P＜0.01).At the same time,the percentage of IFN-γ-producing CD4+memory T cells(TM)in the population aged 18 and above significantly decreased(P＜0.05).Both IL-17a+CD4+T cells and CD4+Teff were significantly higher in adults than adolescents(P＜0.01).Additionally,in the 18-29 age group,peripheral CD4+naive T cells(TN)and CD4+Teff primarily secreted IL-17α,whereas in the population over 30,the percentages of CD4+TM secreting IFN-y decreased(P＜0.000 1),and the two subsets were in balance.These findings suggest that following BCG vaccination,the peripheral antigen-specific Th1,Th17 Teff,and TM 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 TM response may be critical for tuberculosis prevention and control.
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