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首页> 外文期刊>Infection and immunity >Differential Gene Expression in Response to Adjunctive Recombinant Human Interleukin-2 Immunotherapy in Multidrug-Resistant Tuberculosis Patients
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Differential Gene Expression in Response to Adjunctive Recombinant Human Interleukin-2 Immunotherapy in Multidrug-Resistant Tuberculosis Patients

机译：耐药重组结核病患者对重组重组人白介素2免疫治疗的应答​​差异基因表达。

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Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with multidrug chemotherapy to patients with multidrug-resistant tuberculosis (MDR TB) induces measurable changes in in vitro immune response parameters which are associated with changes in the clinical and bacteriologic status of the patients. To determine the molecular basis of these changes, we have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and differential display technology. During rhuIL-2 treatment of MDR TB patients, decreased levels of gamma interferon (IFN-γ) mRNA in peripheral blood mononuclear cells (PBMC) relative to baseline levels were observed. However, at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD), the expression of cellular IFN-γ and IL-2 mRNAs was increased during rhuIL-2 therapy. Levels of other cytokine mRNAs were not significantly affected by rhuIL-2 administration. Using differential-display RT-PCR, we identified several genes expressed at the DTH skin test site which were up- or down-regulated during rhuIL-2 treatment. Cytochrome oxidase type I mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as was heterogeneous nuclear ribonuclear protein G mRNA. CD63, clathrin heavy chain, and β-adaptin mRNAs, all of which encode proteins associated with the endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL-2 administration. The differential effects of IL-2 were confirmed in vitro by using PBMC obtained from PPD-positive individuals stimulated withMycobacterium tuberculosis and IL-2. The differential expression of genes may provide a surrogate marker for leukocyte activation at a mycobacterial antigen-specific response site and for the development of an enhanced antimicrobial response which may result in improved outcomes in MDR TB patients.
机译：将低剂量重组人白介素2（rhuIL-2）与多药化疗联合给予耐多药结核病（MDR TB）患者可诱导可测量的体外免疫应答参数变化，这些参数与临床和细菌学状况的变化有关的病人。为了确定这些变化的分子基础，我们使用了半定量逆转录酶起始PCR（RT-PCR）和差异显示技术。在对耐多药结核病患者进行rhuIL-2治疗期间，观察到外周血单核细胞（PBMC）中的γ干扰素（IFN-γ）mRNA水平相对于基线水平下降。然而，在对结核菌素（PPD）纯化蛋白衍生物的迟发型超敏反应（DTH）反应的部位，在rhuIL-2治疗期间细胞IFN-γ和IL-2 mRNA的表达增加。 rhuIL-2给药未显着影响其他细胞因子mRNA的水平。使用差异显示RT-PCR，我们鉴定了在DTH皮肤测试位点表达的几个基因，在rhuIL-2治疗期间被上调或下调。相对于基线水平，响应rhuIL-2治疗，细胞色素I型mRNA的表达增加，异质核核糖蛋白G mRNA的表达也有所提高。 CD63，网格蛋白重链和β-adaptinmRNAs都编码与细胞内吞液泡途径相关的蛋白质，它们也受到rhuIL-2的调控。通过使用结核分枝杆菌和IL-2刺激的PPD阳性个体的PBMC在体外证实了IL-2的不同作用。基因的差异表达可以为分枝杆菌抗原特异性反应位点上的白细胞活化和增强的抗微生物反应的发展提供替代标志物，这可能导致耐多药结核病患者的预后得到改善。

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