Immunosuppression during active tuberculosis is characterized by decreased interferon-γ production and CD25 expression with elevated forkhead box P3, transforming growth factor-β, and interleukin-4 mRNA levels
Immunosuppression during active tuberculosis is characterized by decreased interferon-γ production and CD25 expression with elevated forkhead box P3, transforming growth factor-β, and interleukin-4 mRNA levels
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DOI：
10.1086/511277
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发表时间：
2007-03-15
影响因子：
6.4
通讯作者：
Walzl, Gerhard
中科院分区：
文献类型：
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作者：
Roberts, Teri;Beyers, Nulda;Walzl, Gerhard
结核分枝杆菌感染后效应反应和调节反应之间的平衡可能决定结果和进展为活动性疾病。我们研究了卡介苗（BCG）刺激的活动性结核病（TB）患者、治疗6个月后的结核病患者和潜伏性结核感染的健康对照者外周血单个核细胞和全血培养物的效应T细胞和调节性T细胞反应。所有3组均表现出bcg诱导的效应T细胞和调节性T细胞表型的增加，分别由CD4(+)CD25（lo）和CD4(+)CD25(hi) T细胞定义。在活动性疾病患者中，卡介苗刺激诱导的CD25、CD4（+）、CD25（hi）、CTLA-4和干扰素- γ的增加最低。然而，这些病例患者的叉头盒P3、转化生长因子(TGF)- β和白细胞介素(IL)-4 mRNA表达水平最高，T-bet: GATA-3比值较低。各组间IL-4 δ 2、IL-10或tgf - β受体- ii mRNA表达无显著差异。总之，这些结果表明，活动性结核患者在分枝杆菌刺激后出现的免疫抑制与自然发生的调节性T细胞有关。
The balance between effector and regulatory responses after Mycobacterium tuberculosis infection may dictate outcome and progression to active disease. We investigated effector and regulatory T cell responses in bacille Calmette-Guerin (BCG)-stimulated peripheral blood mononuclear cells and whole blood cultures from persons with active tuberculosis (TB), persons with TB at the end of 6 months of treatment, and healthy control subjects with latent TB infection. All 3 groups displayed BCG-induced increases in effector and regulatory T cell phenotypes as defined by CD4(+)CD25(lo) and CD4(+)CD25(hi) T cells, respectively. In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4(+)CD25(hi), CTLA-4, and interferon-gamma. However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)-beta, and interleukin (IL)-4 and a lower T-bet: GATA-3 ratio. There were no significant differences in IL-4 delta 2, IL-10, or TGF-beta receptor-II mRNA expression between groups. Together, these results suggest that immunosuppression seen after mycobacterial stimulation in case patients with active TB is associated with naturally occurring regulatory T cells.