Buldeo S, Murdoch D M, Suchard M S
Department of Molecular Medicine and Haematology, Faculty of Health Sciences and National Health Laboratory Service, University of The Witwatersrand, Johannesburg, South Africa.
Clin Dev Immunol. 2012;2012:308473. doi: 10.1155/2012/308473. Epub 2012 Jun 21.
There is a paucity of data on the pulmonary immune-compartment interferon gamma (IFNγ) response to M. tuberculosis, particularly in settings of high tuberculosis (TB) prevalence and in HIV-coinfected individuals. This data is necessary to understand the diagnostic potential of commercially available interferon gamma release assays (IGRAs) in both the pulmonary immune-compartment and peripheral blood. We used intracellular cytokine staining by flow cytometry to assess the IFNγ response to purified protein derivative (PPD) and early secretory antigen 6 (ESAT6) in induced sputa (ISp) and blood samples from HIV-infected, smear-negative, TB suspects. We found that individuals with active TB disease produced significantly less IFNγ in response to PPD in their induced sputa samples than individuals with non-active TB (control group). This difference was not reflected in the peripheral blood, even within the CD27- CD4+ memory T lymphocyte population. These findings suggest that progression to active TB disease may be associated with the loss of IFNγ secretion at the site of primary infection. Our findings highlight the importance of studying pulmonary immune-compartment M. tuberculosis specific responses to elucidate IFNγ secretion across the spectrum of TB disease.
关于肺部免疫区室对结核分枝杆菌的γ干扰素(IFNγ)反应的数据匮乏,尤其是在结核病(TB)高流行地区以及合并感染HIV的个体中。这些数据对于了解市售γ干扰素释放检测(IGRAs)在肺部免疫区室和外周血中的诊断潜力至关重要。我们采用流式细胞术进行细胞内细胞因子染色,以评估来自HIV感染、涂片阴性的TB疑似患者的诱导痰(ISp)和血液样本中对纯化蛋白衍生物(PPD)和早期分泌抗原6(ESAT6)的IFNγ反应。我们发现,与非活动性TB患者(对照组)相比,活动性TB疾病患者的诱导痰样本对PPD产生的IFNγ显著减少。这种差异在外周血中并未体现,即使在CD27-CD4+记忆性T淋巴细胞群体中也是如此。这些发现表明,进展为活动性TB疾病可能与原发感染部位IFNγ分泌丧失有关。我们的研究结果凸显了研究肺部免疫区室对结核分枝杆菌的特异性反应以阐明整个TB疾病谱中IFNγ分泌情况的重要性。