The association of functionality and phenotype of follicular helper T cells (Tfh) with dengue virus (DENV) specific antibody responses and clinical disease severity has not been well studied. We investigated the phenotype and functionality of Tfh cells and plasmablasts in adult patients (DF = 18, DHF = 22) with acute dengue (day 4 to 8 since onset of fever) of varying severity using multiparametric flowcytometry. The properties of Tfh cells were correlated with viraemia, disease severity, plasmablast responses and DENV-specific serum antibody responses. We further evaluated the kinetics of neutralizing antibodies (Neut50) throughout the course of illness in order to evaluate their association with clinical disease severity and viraemia. Tfh cells (especially those producing IL-21 and co-expressing PD-1 and ICOS) were found to be significantly expanded (p < 0.0001) and highly activated in patients with DHF compared to those with DF. The frequency of Tfh cells significantly correlated with DENV-specific IgG, NS1-specific antibodies and Neut50 antibody titres in patients with DHF but not in those with DF. Although the Neut50 titres increased during the course of acute secondary DENV infection, they showed differences based on serotype. For instance, the Neut50 titres were significantly higher during the latter part of illness in patients with DF compared to DHF in DENV1 infection, while in DENV2, patients with DHF had significantly higher titres. The viral loads during early illness did not correlate with the subsequent rise in the Neut50 antibody titres during any time point of illness. The expansion of Tfh cells is associated with DHF and DENV-specific IgG, NS1-specific and neutralizing antibodies. Neut50 titres did not associate with disease severity or viraemia at the point of first presentation during the febrile phase, but later titres do show differential association with severity in patients with DENV1 compared to DENV2.

中文翻译：

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急性登革热感染患者滤泡辅助性T细胞的表型和功能。

卵泡辅助性T细胞（Tfh）的功能和表型与登革病毒（DENV）特异性抗体反应和临床疾病严重程度之间的关联尚未得到很好的研究。我们使用多参数流式细胞术研究了严重程度不同的急性登革热（自发烧后第4至8天）的成年患者（DF = 18，DHF = 22）的Tfh细胞和成纤维细胞的表型和功能。Tfh细胞的特性与病毒血症，疾病严重程度，成浆细胞反应和DENV特异性血清抗体反应相关。我们进一步评估了整个疾病过程中中和抗体（Neut50）的动力学，以评估其与临床疾病严重程度和病毒血症的关联。与DF的患者相比，DHF患者的Tfh细胞（尤其是产生IL-21并共同表达PD-1和ICOS的细胞）显着扩增（p <0.0001）并高度活化。在DHF患者中，Tfh细胞的频率与DENV特异性IgG，NS1特异性抗体和Neut50抗体滴度显着相关，而在DF患者中则不然。尽管在急性继发性DENV感染过程中Neut50滴度有所增加，但它们根据血清型显示出差异。例如，在DENV1感染中，DF患者患病后期的Neut50滴度明显高于DHF，而在DENV2中，DHF患者滴度显着较高。在疾病的任何时间点，早期疾病期间的病毒载量与随后的Neut50抗体滴度的升高均不相关。Tfh细胞的扩增与DHF和DENV特异性IgG，NS1特异性和中和抗体有关。Neut50滴度在高热期首次出现时与疾病的严重程度或病毒血症无关，但与DENV2相比，后来的滴度确实显示出与DENV2患者的严重程度存在差异。