Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection
Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection
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DOI：
10.1002/eji.201040455
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发表时间：
2010-08-01
影响因子：
5.4
通讯作者：
Dieli, Francesco
中科院分区：
文献类型：
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作者：
Caccamo, Nadia;Guggino, Giuliana;Dieli, Francesco
Th 1 CD 4（+）T细胞及其衍生的细胞因子对于预防结核分枝杆菌至关重要。使用多参数流式细胞术，我们评估了潜伏性M患者中CD 4（+）T细胞的7种不同功能状态（IFN-γ/IL-2/TNF-α三重表达，IFN-γ/IL-2，IFN-γ/TNF-α或TNF-α/IL-2双表达或IFN-γ，IL-2或TNF-α单表达）的分布。结核感染（LTBI）和活动性结核（TB）。我们发现，虽然在85- 90%的TB患者中可检测到三重表达，但仅在10-15%的LTBI受试者中存在。相反，与其他CD 4（+）T细胞亚群相比，LTBI受试者的IL-2/IFN-γ双表达者和IFN-γ单表达者的比例显著更高（12- 15倍）。其他双或单CD 4（+）T细胞表达者的比例在TB和LTBI受试者之间没有差异。这些不同的IFN-γ，IL-2和TNF-α谱M。结核病特异性CD 4（+）T细胞似乎与活菌负荷相关，如结核病感染患者完成抗分枝杆菌治疗后多功能T细胞频率降低所示。我们的研究结果表明，CD 4（+）T细胞的表型和功能特征可能作为保护和治疗宿主反应的免疫相关性，并成为一个有用的工具，以监测抗分枝杆菌治疗的疗效。
Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametic flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4(+) T-cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.