One of the greatest challenges in Chagas disease research is the search for tools that will enable the assessment of pharmacological treatment efficacy. A recently described set of serological biomarkers composed of four parasite antigens and established criteria of treatment efficacy allowed the evaluation of the impact of benznidazole treatment a short/medium time after the treatment. In addition, cellular immunological parameters have also been described as potential indicators of the treatment response. The cytotoxic CD8+ T cells specific to five epitopes in the PFR2, PFR3, TcCA-2 and KMP11 antigens have been analysed, and these epitopes have been shown to be recognized, processed and presented in the context of a natural T. cruzi infection. In the present manuscript, we characterized these antigen-specific CD8+ T cells in indeterminate chronic Chagas disease patients both before and after (from 11 to 28 months) benznidazole treatment. The results indicate that there is a differential memory CD8+ T cell profile depending on the antigenic epitope and that the benznidazole treatment modulates the memory, differentiation and senescence phenotypes of the epitope-specific CD8+ T cells. Moreover, in these patients, the reactivity of sera against the referred set of biomarkers was evaluated. The data obtained show that the patients who met the established therapeutic efficacy criteria presented a differential phenotypic profile of the antigen-specific CD8+ T cells even prior to treatment compared to the patients who did not meet the therapeutic efficacy criteria, and this behaviour is associated with a better functionality of these CD8+ T cells.

中文翻译：

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苯硝唑治疗的慢性无症状Chagas病患者中表位特异性细胞毒性CD8 + T细胞的表型和功能差异。

查加斯病研究的最大挑战之一是寻找能够评估药理治疗功效的工具。最近描述的一组由四种寄生虫抗原组成的血清学生物标志物和已确立的治疗功效标准允许在治疗后的短/中时间评估苯并硝唑治疗的影响。另外，细胞免疫学参数也已被描述为治疗反应的潜在指标。已经分析了对PFR2，PFR3，TcCA-2和KMP11抗原中的五个表位具有特异性的细胞毒性CD8 + T细胞，并且这些表位已显示出在自然克鲁氏杆菌感染的情况下被识别，加工和呈递。在本手稿中，我们在不确定的慢性恰加斯病患者中，对苯甲硝唑治疗前后（11到28个月）表征了这些抗原特异性CD8 + T细胞。结果表明，取决于抗原表位，存在差异记忆CD8 + T细胞谱，并且苯并咪唑处理可调节表位特异性CD8 + T细胞的记忆，分化和衰老表型。此外，在这些患者中，评估了血清对所提及的一组生物标志物的反应性。所获得的数据表明，达到既定疗效标准的患者与未达到疗效标准的患者相比，甚至在治疗前就已经表现出抗原特异性CD8 + T细胞的不同表型特征，