Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil.
Department of Health Education, Federal University of Sergipe, Lagarto, Brazil.
Front Immunol. 2018 Dec 12;9:2920. doi: 10.3389/fimmu.2018.02920. eCollection 2018.
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.
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。