Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Front Immunol. 2020 Sep 24;11:1980. doi: 10.3389/fimmu.2020.01980. eCollection 2020.
The protective or pathogenic role of T lymphocytes during the acute phase of dengue virus (DENV) infection has not been fully understood despite its importance in immunity and vaccine development. This study aimed to clarify the kinetics of T lymphocyte subsets during the clinical course of acute dengue patients. In this hospital-based cohort study, 59 eligible Vietnamese dengue patients were recruited and admitted. They were investigated and monitored for T cell subsets and a panel of clinical and laboratory parameters every day until discharged and at post-discharge from the hospital. We described for the first time the kinetics of T cell response during the clinical course of DENV infection. Severe cases showed significantly lower levels of effector CD8 T cells compared to mild cases at day -1 ( = 0.017) and day 0 ( = 0.033) of defervescence. After defervescence, these cell counts in severe cases increased rapidly to equalize with the levels of mild cases. Our results also showed a decline in total CD4 T, Th1, Th1/17 cells during febrile phase of dengue patients compared to normal controls or convalescent phase. On the other hand, Th2 cells increased during DENV infection until convalescent phase. Cytokines such as interferon-γ, IL-12p70, IL-5, IL-23, IL-17A showed tendency to decrease on day 0 and 1 compared with convalescence and only IL-5 showed significance indicating the production during acute phase was not systemic. With a rigorous study design, we uncovered the kinetics of T cells in natural DENV infection. Decreased number of effector CD8 T cells in the early phase of infection and subsequent increment after defervescence day probably associated with the T cell migration in DENV infection.
尽管 T 淋巴细胞在免疫和疫苗开发中具有重要作用,但在登革病毒(DENV)感染急性期,其保护或致病作用仍未完全阐明。本研究旨在阐明急性登革热患者临床病程中 T 淋巴细胞亚群的变化。在这项基于医院的队列研究中,共招募了 59 名符合条件的越南登革热患者,并对他们进行了调查和监测,每天监测 T 细胞亚群和一系列临床及实验室参数,直至出院和出院后。我们首次描述了 DENV 感染临床过程中 T 细胞反应的动力学。与轻症病例相比,在退热的第-1 天(=0.017)和第 0 天(=0.033),重症病例的效应性 CD8 T 细胞水平明显较低。退热后,重症病例的这些细胞计数迅速增加,与轻症病例的水平相持平。我们的研究结果还表明,与正常对照或恢复期相比,登革热患者在发热期总 CD4 T、Th1、Th1/17 细胞数量下降。另一方面,在 DENV 感染期间,Th2 细胞增加,直到恢复期。与恢复期相比,干扰素-γ、IL-12p70、IL-5、IL-23、IL-17A 等细胞因子在第 0 天和第 1 天有下降的趋势,但只有 IL-5 有显著差异,表明急性期的产生不是全身性的。通过严格的研究设计,我们揭示了自然 DENV 感染中 T 细胞的变化。感染早期效应性 CD8 T 细胞数量减少,退热后数量增加,这可能与 T 细胞在 DENV 感染中的迁移有关。