AbstractIntroductionAlthough the role of dengue virus (DENV)‐specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus‐specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of DENV–NS3 and DENV–NS5 protein‐specific T cells differ in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF).MethodsUsing intracellular cytokine assays, we assessed the production of interferon γ (IFNγ), tumor necrosis factor‐α (TNF‐α), macrophage inflammatory protein‐1β (MIP‐1β), and CD107a expression in adult patients with acute DF (n = 21) and DHF (n = 22).ResultsQuadruple cytokine‐producing, polyfunctional DENV–NS3‐ and DENV–NS5‐specific T cells were more frequent in those with DF when compared to those with DHF. While DENV–NS3‐ and DENV–NS5‐specific T cells in patients with DF expressed IFNγ > TNF‐α > MIP‐β > CD107a, T cells of those with DHF predominantly expressed CD107a > MIP‐1β > IFNγ > TNF‐α. Overall production of IFNγ or TNF‐α by DENV–NS3‐ and DENV–NS5‐specific T cells was significantly higher in patients with DF. The majority of NS3‐specific T cells in patients with DF (78.6%) and DHF (68.9%) were single‐cytokine producers; 76.6% of DENV–NS5‐specific T cells in those with DF and 77.1% of those with DHF, produced only a single cytokine. However, no significant association was found with polyfunctional T‐cell responses and the degree of viraemia.ConclusionsOur results suggest that the functional phenotype of DENV‐specific T cells are likely to associate with clinical disease severity.

中文翻译：

---

登革热病毒特异性多功能 T 细胞反应与急性登革热感染临床疾病严重程度的关系

摘要介绍尽管登革热病毒 (DENV) 特异性 T 细胞在急性登革热感染发病机制中的作用正在逐渐显现，但与较轻临床疾病相关的病毒特异性 T 细胞的功能尚未得到充分研究。我们试图研究登革热 (DF) 和登革出血热 (DHF) 患者中 DENV-NS3 和 DENV-NS5 蛋白特异性 T 细胞的功能有何不同。方法使用细胞内细胞因子测定，我们评估了成人急性 DF 患者中干扰素 γ (IFNγ)、肿瘤坏死因子 α (TNF-α)、巨噬细胞炎症蛋白 1β (MIP-1β) 和 CD107a 的表达（n = 21) 和 DHF (n = 22)。结果与 DHF 患者相比，DF 患者中产生四重细胞因子、多功能 DENV-NS3 和 DENV-NS5 特异性 T 细胞的频率更高。DF 患者中的 DENV-NS3 和 DENV-NS5 特异性 T 细胞表达 IFNγ > TNF-α > MIP-β > CD107a，而 DHF 患者的 T 细胞主要表达 CD107a > MIP-1β > IFNγ > TNF-α。DF 患者中 DENV-NS3 和 DENV-NS5 特异性 T 细胞产生的 IFNγ 或 TNF-α 总体产量显着较高。DF (78.6%) 和 DHF (68.9%) 患者中的大多数 NS3 特异性 T 细胞是单细胞因子产生者；DF 患者中 76.6% 的 DENV-NS5 特异性 T 细胞和 DHF 患者中 77.1% 的 T 细胞仅产生单一细胞因子。然而，未发现多功能 T 细胞反应与病毒血症程度之间存在显着关联。结论我们的结果表明 DENV 特异性 T 细胞的功能表型可能与临床疾病严重程度相关。