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重组抗原诱导多功能 T 淋巴细胞高表达,有望成为麻风病特异性疫苗。

Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy.

机构信息

Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil.

Department of Health Education, Federal University of Sergipe, Lagarto, Brazil.

出版信息

Front Immunol. 2018 Dec 12;9:2920. doi: 10.3389/fimmu.2018.02920. eCollection 2018.

Abstract

Leprosy is a chronic disease caused by infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts ( cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against infection that prevents the development of leprosy. These data further our understanding of infection/leprosy and are instructive for vaccine development.

摘要

麻风病是一种由 感染引起的慢性疾病,可导致严重的神经并发症和身体残疾。麻风病特异性疫苗将是控制计划中的一个重要组成部分,但仍缺乏这种疫苗。鉴于多功能 CD4 T 细胞(即能够同时分泌干扰素(IFN)-γ、白细胞介素(IL)-2 和肿瘤坏死因子(TNF)的组合的细胞)现已被牵连到几种感染的保护性反应中,我们测试了这样一个假设,即重组 抗原特异性多功能 T 细胞在麻风病患者及其健康接触者之间是否存在差异。我们使用全血测定法和外周血单核细胞来表征 39 例少菌型(PB)和 17 例多菌型(MB)麻风病患者和 31 名健康家庭接触者(HHC)的抗原特异性 T 细胞反应。将细胞与粗制分枝杆菌提取物(细胞超声-MLCS)和纯化蛋白衍生物(PPD)或重组 ML2028 蛋白( Ag85B 的同源物)孵育。多重分析显示 HHC 和 PB 中的细胞对 IFN-γ和 IL-2 的抗原特异性产生,证实了这些个体中的 Th1 偏向性。多参数流式细胞术随后显示,在 HHC 中观察到的多功能 ML2028 特异性 T 细胞群体大于在 PB 患者中观察到的群体。综上所述,我们的数据表明,这些多功能抗原特异性 T 细胞提供了针对 感染的更有效的反应,从而防止了麻风病的发展。这些数据进一步了解了 感染/麻风病,并为疫苗开发提供了指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb5/6315144/4bd577b33e1b/fimmu-09-02920-g0001.jpg

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