In the absence of a more effective vaccine against TB and in the interest of developing one, it is essential to understand immune responses associated with BCG protection. We comprehensively characterized T cell populations in BCG-vaccinated children over time. Blood from 78 healthy, BCG-vaccinated children representing four age groups (<1 yr, ≥1 yr <2 yr, ≥2 yr <5 yr, ≥5 yr), was stimulated in vitro for 24 hours and 6 days with live BCG to induce effector and central memory responses. Antigen-specific CD4, CD8, γδ and regulatory T cell populations were phenotyped and intracellular and secreted cytokines measured by flow cytometry and multiplex ELISA respectively. Our results demonstrated that populations of naïve T cells predominated in infants, compared to older children. However, BCG-specific effector CD4 T cell responses were equivalent and antigen-specific CD4 T cell proliferative capacity was increased in infants compared to older children. Increases in innate immune responses including γδ T cell responses and secreted pro-inflammatory cytokines were noted with increasing age. In conclusion, we identified that the capacity to expand and differentiate effector T cells in response to BCG stimulation wanes with increasing age, which may indicate waning central memory immunity. Booster vaccination could be considered to maintain the antigen-specific central memory pool and possibly enhance the duration of protection.

中文翻译：

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健康儿童对 BCG 的免疫反应与年龄相关的减弱支持在结核病流行国家需要加强剂量的 BCG。

在没有更有效的结核病疫苗的情况下，为了开发一种疫苗，了解与卡介苗保护相关的免疫反应至关重要。随着时间的推移，我们全面描述了接种 BCG 的儿童的 T 细胞群。来自代表四个年龄组（<1 岁、≥1 岁 <2 岁、≥2 岁 <5 岁、≥5 岁）的 78 名接种了 BCG 的健康儿童的血液在体外用活 BCG 刺激 24 小时和 6 天诱导效应和中枢记忆反应。对抗原特异性 CD4、CD8、γδ 和调节性 T 细胞群进行表型分析，并分别通过流式细胞术和多重 ELISA 测量细胞内和分泌的细胞因子。我们的研究结果表明，与年龄较大的儿童相比，幼稚 T 细胞群在婴儿中占主导地位。然而，与年龄较大的儿童相比，婴儿的 BCG 特异性效应 CD4 T 细胞反应相当，并且抗原特异性 CD4 T 细胞增殖能力增加。随着年龄的增长，包括γδT细胞反应和分泌的促炎细胞因子在内的先天免疫反应增加。总之，我们发现响应 BCG 刺激而扩增和分化效应 T 细胞的能力随着年龄的增长而减弱，这可能表明中枢记忆免疫减弱。可以考虑加强疫苗接种以维持抗原特异性中央记忆库并可能延长保护持续时间。随着年龄的增长，包括γδT细胞反应和分泌的促炎细胞因子在内的先天免疫反应增加。总之，我们发现响应 BCG 刺激而扩增和分化效应 T 细胞的能力随着年龄的增长而减弱，这可能表明中枢记忆免疫减弱。可以考虑加强疫苗接种以维持抗原特异性中央记忆库并可能延长保护持续时间。随着年龄的增长，包括γδT细胞反应和分泌的促炎细胞因子在内的先天免疫反应增加。总之，我们发现响应 BCG 刺激而扩增和分化效应 T 细胞的能力随着年龄的增长而减弱，这可能表明中枢记忆免疫减弱。可以考虑加强疫苗接种以维持抗原特异性中央记忆库并可能延长保护持续时间。