Polarization of PPD-specific T-cell response of patients with tuberculosis from Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-α or interleukin-12
Polarization of PPD-specific T-cell response of patients with tuberculosis from Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-α or interleukin-12
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DOI：
10.1165/ajrcmb.24.2.4274
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发表时间：
2001-02-01
影响因子：
6.4
通讯作者：
Del Prete, G
中科院分区：
文献类型：
--
作者：
Marchant, A;Amedei, A;Del Prete, G
辅助性T细胞（Th）1/Th 2平衡的T淋巴细胞反应纯化蛋白衍生物（PPD）在克隆水平进行了评估，在6个意大利和冈比亚肺结核（TB）患者抗分枝杆菌治疗前后，以及在5冈比亚和4个意大利健康的免疫对照组。在未经治疗的患者中，来自外周血或胸腔积液的大多数PPD特异性克隆显示出Th 0细胞因子谱（产生干扰素[IFN]-γ和白细胞介素[IL]-4/IL-5）。在6个月的治疗和临床愈合后，大多数PPD特异性克隆在意大利和冈比亚患者中显示出极化的Th 1特征（产生IFN-γ，但不产生IL-4/IL-5）。Th 1极化在冈比亚比意大利患者中不明显，并且在另一组经历治疗失败的4名意大利患者中未发生。结核病患者成功治疗后观察到的细胞因子谱与健康对照受试者中发现的细胞因子谱相似，PPD刺激培养物产生的特异性不确定的T细胞克隆在冈比亚个体和治疗失败的意大利患者中显示出类似的Th 0/Th 2偏好。治疗前冈比亚患者的Th 0/Th 2偏置反应可以在体外由IFN-α或IL-12调节，其诱导PPD特异性和旁观者T细胞的Th 1极化。我们的数据表明，活动性结核病与占主导地位的Th 0对分枝杆菌抗原的反应，可能在疾病的发病机制中发挥作用。使用Th 1极化细胞因子的辅助免疫疗法可以增加宿主对分枝杆菌的防御并加速愈合。
The T helper (Th) 1/Th2 balance in the T-lymphocyte response to purified protein derivative (PPD) was evaluated at the clonal level in six Italian and five Gambian patients with pulmonary tuberculosis (TB) before and after antimycobacterial therapy, as well as in five Gambian and four Italian healthy immune control subjects. In untreated patients, most PPD-specific clones derived from either peripheral blood or pleural effusions showed a Th0 cytokine profile (production of both interferon [IFN]-gamma and interleukin [IL]-4/IL-5). After 6 mo of therapy and clinical healing, most PPD-specific clones showed a polarized Th1 profile (production of IFN-gamma but not IL-4/IL-5) in both Italian and Gambian patients. The Th1 polarization was less marked in Gambian than in Italian patients and failed to occur in another group of four Italian patients who experienced treatment failure. The cytokine profile observed after successful therapy in patients with TB was similar to that found in healthy control subjects, T-cell clones of undefined specificity generated from PPD-stimulated cultures showed a similar Th0/Th2 bias in Gambian individuals and Italian patients with treatment failure. The Th0/Th2-biased responses in Gambian patients before therapy could be modulated in vitro by IFN-alpha or IL-12, which induced a Th1 polarization of both PPD-specific and bystander T cells. Our data show that active TB associates with a predominant Th0 response to mycobacterial antigens that could play a role in the pathogenesis of the disease. Adjunctive immunotherapy using Th1-polarizing cytokines could increase host defense against mycobacteria and accelerate healing.