Specific T Cell Frequency and Cytokine Expression Profile Do Not Correlate with Protection against Tuberculosis after Bacillus Calmette-Guerin Vaccination of Newborns
Specific T Cell Frequency and Cytokine Expression Profile Do Not Correlate with Protection against Tuberculosis after Bacillus Calmette-Guerin Vaccination of Newborns
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DOI：
10.1164/rccm.201003-0334oc
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发表时间：
2010-10-15
影响因子：
24.7
通讯作者：
Hanekom, Willem A.
中科院分区：
文献类型：
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作者：
Kagina, Benjamin M. N.;Abel, Brian;Hanekom, Willem A.
新的结核病疫苗的免疫原性通常是通过测量T细胞的频率和细胞因子表达谱来评估的。目的：我们测试了这一结果是否与新生儿接种卡介苗(BCG)后预防儿童结核病有关。方法：10周龄婴儿出生时常规接种卡介苗，全血与卡介苗孵育12小时，然后冷冻保存进行细胞内细胞因子分析。对婴儿进行了两年的跟踪调查，以确定哪些婴儿患上了培养阳性结核病，这些婴儿被认为对结核病没有保护作用。尽管在家庭中接触了结核病，但没有患上结核病的婴儿，以及另一组随机选择的从未被评估是否患有结核病的婴儿，也被确定为这些组被认为是预防结核病的。从这些组中解冻细胞，用流式细胞术检测CD4、CD8和γ-T细胞特异性的干扰素-γ、肿瘤坏死因子-α、IL-2和IL-17的表达。测量和主要结果：共纳入5662名婴儿，29名未保护婴儿和两组55名受保护婴儿。在三组婴儿中，卡介苗特异性的CD4、CD8和Gamma-Delta T细胞的频率没有差异。尽管卡介苗诱导了复杂的细胞内细胞因子表达模式，但保护婴儿和未保护婴儿之间没有差异。结论：分枝杆菌特异性T细胞的频率和细胞因子谱与预防结核病无关。抗结核分枝杆菌免疫的关键成分，如CD4T细胞干扰素-γ的产生，可能不一定转化为预防结核病的免疫相关因素。
Rationale Immunogenicity of new tuberculosis (TB) vaccines is commonly assessed by measuring the frequency and cytokine expression profile of T cells.Objectives: We tested whether this outcome correlates with protection against childhood TB disease after newborn vaccination with bacillus Calmette-Guerin (BCG).Methods: Whole blood from 10-week-old infants, routinely vaccinated with BCG at birth, was incubated with BCG for 12 hours, followed by cryopreservation for intracellular cytokine analysis. Infants were followed for 2 years to identify those who developed culture-positive TB these infants were regarded as not protected against TB. Infants who did not develop TB disease despite exposure to TB in the household, and another group of randomly selected infants who were never evaluated for TB, were also identified these groups were regarded as protected against TB. Cells from these groups were thawed, and CD4, CD8, and gamma delta T cell-specific expression of IFN-gamma, TNF-alpha, IL-2, and IL-17 measured by flow cytometry.Measurements and Main Results: A total of 5,662 infants were enrolled; 29 unprotected and two groups of 55 protected infants were identified. There was no difference in frequencies of BCG-specific CD4, CD8, and gamma delta T cells between the three groups of infants. Although BCG induced complex patterns of intracellular cytokine expression, there were no differences between protected and unprotected infants.Conclusions: The frequency and cytokine profile of mycobacteria-specific T cells did not correlate with protection against TB. Critical components of immunity against Mycobacterium tuberculosis, such as CD4 T cell IFN-gamma production, may not necessarily translate into immune correlates of protection against TB disease.