Laboratorio de Inmunología de Enfermedades Infecciosas, Instituto de Biomedicina, Universidad Central de Venezuela, Caracas, Venezuela.
Hum Immunol. 2010 Nov;71(11):1099-104. doi: 10.1016/j.humimm.2010.07.006. Epub 2010 Aug 2.
The control of mycobacterial infection by the host depends on cell-mediated immunity (CMI), involving activated macrophages, T cells, and type 1 cytokines (Th1). Here we evaluated the capacity of antigen-induced proliferation by peripheral blood mononuclear cells (PBMCs) and the production of proinflammatory tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12p40). The Th1 cytokine interferon-gamma (IFN-γ) and Th2 cytokines interleukin 4 (IL-4) and interleukin 5 (IL-5) in 62 pulmonary tuberculosis (TB) patients (40 Warao indigenous patients [WP] and 22 Creole non-indigenous patients [CP]) and 24 healthy controls (12 Warao indigenous controls [WC] and 12 Creole non-indigenous controls [CC]) at 24 and 48 hours in response to purified protein derivative (PPD) from Mycobacterium tuberculosis. The overall results revealed that testing of CP and CC' PBMCs for TNF-α, IFN-γ, and IL-12p40 production was higher compared with WP and WC' PBMCs after stimulating for 24 and 48 hours (p < 0.0001), within the WP group, the lower productions of IL-12p40 and IFN-γ significantly correlated (r(2) = 0.91, p < 0.01). Although in general there was interindividual variability in the observed responses of Th2 cytokines, especially with IL-4, there was a trend to produce higher PPD-induced IL-5 by WP' PBMCs compared with WC' PBMCs and CP' PBMCs at 24 and 48 hours, respectively. High IL-5 production correlated inversely with low IFN-γ production (r(2) = -0.97, p < 0.002). In conclusion, our results suggest that PPD-induced responses observed in patients from both populations can be divided into two groups: one group that activates Creole' PBMCs to preferentially secrete TNF-α, IL-12p40 and IFN-γ and another group that activates preferential secretion of IL-5 in Warao' PBMCs.
宿主对分枝杆菌感染的控制依赖于细胞介导的免疫（CMI），涉及激活的巨噬细胞、T 细胞和 1 型细胞因子（Th1）。在这里，我们评估了外周血单核细胞（PBMC）的抗原诱导增殖能力以及前炎症性肿瘤坏死因子-α（TNF-α）和白细胞介素 12（IL-12p40）的产生。在 62 例肺结核（TB）患者（40 名瓦劳土著患者[WP]和 22 名克里奥尔非土著患者[CP]）和 24 名健康对照者（12 名瓦劳土著对照者[WC]和 12 名克里奥尔非土著对照者[CC]）中，在 24 小时和 48 小时时，用结核分枝杆菌纯化蛋白衍生物（PPD）刺激后，检测了 Th1 细胞因子干扰素-γ（IFN-γ）和 Th2 细胞因子白细胞介素 4（IL-4）和白细胞介素 5（IL-5）。总体结果表明，与 WP 和 WC 的 PBMC 相比，CP 和 CC 的 PBMC 在 24 小时和 48 小时刺激后产生 TNF-α、IFN-γ和 IL-12p40 的检测值更高（p<0.0001），在 WP 组中，IL-12p40 和 IFN-γ的低产量呈显著相关（r²=0.91，p<0.01）。尽管观察到 Th2 细胞因子的反应存在个体间的变异性，尤其是 IL-4，但 WP 的 PBMC 在 24 小时和 48 小时时分别比 WC 的 PBMC 和 CP 的 PBMC 产生更高的 PPD 诱导的 IL-5 的趋势。高 IL-5 产量与低 IFN-γ产量呈负相关（r²=-0.97，p<0.002）。总之，我们的结果表明，来自两个群体的患者中观察到的 PPD 诱导反应可以分为两组：一组激活克里奥尔人的 PBMC 优先分泌 TNF-α、IL-12p40 和 IFN-γ，另一组激活瓦劳人的 PBMC 优先分泌 IL-5。
