Servei de Microbiologia, Hospital Universitari Germans Trias i Pujol, Institut d'Investigació Germans Trias i Pujol, Barcelona, Spain.
CIBER Enfermedades Respiratorias, CIBERES, Instituto de Salud Carlos III, Madrid, Spain.
Front Immunol. 2019 Jan 9;9:3094. doi: 10.3389/fimmu.2018.03094. eCollection 2018.
The immunological characterization of different cell markers has opened the possibility of considering them as immune tools for tuberculosis (TB) management, as they could correlate with TB latency/disease status and outcome. CD4 T-cells producing IFN-γ with a low expression of CD27 have been described as an active TB marker. In addition, there are unknown homing receptors related to TB, such as CCR4, which might be useful for understanding TB pathogenesis. The aim of our study is focused on the assessment of several T-cell subsets to understand immune-mechanisms in TB. This phenotypic immune characterization is based on the study of the specific immune responses of T-cells expressing CD27 and/or CCR4 homing markers. Subjects enrolled in the study were: (i) 22 adult patients with active TB, and (ii) 26 individuals with latent TB infection (LTBI). Blood samples were drawn from each patient. The expression of CD27 and/or CCR4 markers were analyzed within CD4 T-cells producing: (i) IFN-γ, (ii) TNF-α, (iii) TNF-αIFN-γ, and (iv) IFN-γ and/or TNF-α. The percentage of CD27 within all CD4 T-cell populations analyzed was significantly higher on active TB compared to LTBI after PPD or ESAT-6/CFP-10 stimulation. As previously reported, a ratio based on the CD27 median fluorescence intensity (MFI) was also explored (MFI of CD27 in CD4 T-cells over MFI of CD27 in IFN-γCD4 T-cells), being significantly increased during disease ( < 0.0001 after PPD or ESAT-6/CFP-10 stimulation). This ratio was also assessed on the other CD4 T-cells functional profiles after specific stimulation, being significantly associated with active TB. Highest diagnostic accuracies for active TB (AUC ≥ 0.91) were achieved for: (i) CD27 within IFN-γTNF-αCD4 T-cells in response to ESAT-6/CFP-10, (ii) CD27 and CCR4 markers together within IFN-γCD4 T-cells in response to PPD, and (iii) CD27 MFI ratio performed on IFN-γTNF-αCD4 T-cells after ESAT-6/CFP-10 stimulation. The lowest diagnostic accuracy was observed when CCR4 marker was evaluated alone (AUC ≤ 0.77). CD27 and CCR4 expression detection could serve as a good method for immunodiagnosis. Moreover, the immunological characterization of markers/subset populations could be a promising tool for understanding the biological basis of the disease.
不同细胞标志物的免疫学特征为将其作为结核病（TB）管理的免疫工具提供了可能，因为它们可以与 TB 潜伏期/疾病状态和结果相关。已经描述了表达 IFN-γ且 CD27 表达水平低的 CD4 T 细胞作为活动性 TB 的标志物。此外，还有与 TB 相关的未知归巢受体，如 CCR4，这可能有助于了解 TB 的发病机制。我们的研究目的是评估几种 T 细胞亚群，以了解 TB 中的免疫机制。这种表型免疫特征基于对表达 CD27 和/或 CCR4 归巢标志物的 T 细胞的特定免疫反应的研究。纳入研究的受试者为：（i）22 名活动性 TB 成年患者，和（ii）26 名潜伏性 TB 感染（LTBI）个体。从每位患者抽取血样。在产生：（i）IFN-γ、（ii）TNF-α、（iii）TNF-αIFN-γ 和（iv）IFN-γ和/或 TNF-α的 CD4 T 细胞内分析 CD27 和/或 CCR4 标志物的表达。在 PPD 或 ESAT-6/CFP-10 刺激后，与 LTBI 相比，所有分析的 CD4 T 细胞群中 CD27 的百分比在活动性 TB 中明显更高。如前所述，还探索了基于 CD27 中值荧光强度（MFI）的比值（CD4 T 细胞中 CD27 的 MFI 除以 IFN-γCD4 T 细胞中 CD27 的 MFI），在疾病期间显著增加（<0.0001，在 PPD 或 ESAT-6/CFP-10 刺激后）。在特定刺激后对其他 CD4 T 细胞功能谱也评估了该比值，与活动性 TB 显著相关。活动性 TB 的最高诊断准确性（AUC≥0.91）是通过以下方法获得的：（i）ESAT-6/CFP-10 刺激后 IFN-γTNF-αCD4 T 细胞中的 CD27，（ii）PPD 刺激后 IFN-γCD4 T 细胞中 CD27 和 CCR4 标志物的组合，和（iii）ESAT-6/CFP-10 刺激后 IFN-γTNF-αCD4 T 细胞中 CD27 MFI 比值。当单独评估 CCR4 标志物时，观察到最低的诊断准确性（AUC≤0.77）。CD27 和 CCR4 的表达检测可作为免疫诊断的良好方法。此外，标志物/亚群的免疫特征可以成为了解疾病生物学基础的有前途的工具。
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