INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Paris, France.
INSERM U955, équipe 16, Vaccine Research Institute, Faculté de Médecine, Université Paris Est Créteil, Créteil, France.
J Virol. 2019 Jun 14;93(13). doi: 10.1128/JVI.02321-18. Print 2019 Jul 1.
Human herpesvirus 6 (HHV-6) infects >90% of the population and establishes a latent infection with asymptomatic episodes of reactivation. However, HHV-6 reactivation is associated with morbidity and sometimes mortality in immunocompromised patients. To date, control of the virus in healthy virus carriers and the failure to control it in patients with disease remain poorly understood. In particular, knowledge of HHV-6-specific T-cell responses is limited. Here, we characterized HHV-6A- and HHV-6B-specific CD4 and CD8 T-cell responses from peripheral blood mononuclear cells (PBMCs) of healthy donors. We studied the phenotype of effector HHV-6-specific T cells , as well as of induced specific suppressive regulatory CD4 T cells poststimulation, in comparison to human cytomegalovirus (HCMV) responses. Compared to that for HCMV, we show that T-cell reactivity in peripheral blood is detectable but at very low frequency, both for HHV-6A and -6B viruses. Interestingly, the phenotype of the specific T cells also differs between the viruses. HHV-6A- and HHV-6B-specific CD4 T lymphocytes are less differentiated than HCMV-specific T cells. Furthermore, we show a higher frequency of HHV-6-specific suppressive regulatory T cells (eTregs) than HCMV-specific eTregs in coinfected individuals. Despite the strong similarity of HHV-6 and HCMV from a virologic point of view, we observed immunological differences, particularly in relation to the frequency and phenotype of effector/memory and regulatory virus-specific T cells. This suggests that different immune factors are solicited in the control of HHV-6 infection than in that of HCMV infection. T cells are central to an effective defense against persistent viral infections that can be related to human cytomegalovirus (HCMV) or human herpesvirus 6 (HHV-6). However, knowledge of HHV-6-specific T-cell responses is limited. In order to deepen our knowledge of T-cell responses to HHV-6, we characterized HHV-6A- and HHV-6B-specific CD4 and CD8 T-cell responses directly from healthy coinfected blood donors. Despite the strong similarity of HHV-6 and HCMV from a virologic point of view, we observed immunological differences, particularly in relation to the frequency and phenotype of effector/memory and regulatory virus-specific T cells. This suggests that different immune factors are solicited in the control of HHV-6 infection than in that of HCMV infection. Our findings may encourage immunomonitoring of patients with viral replication episodes to follow the emergence of effector versus regulatory T cells.
人类疱疹病毒 6（HHV-6）感染超过 90%的人群，并建立潜伏感染，无症状再激活。然而，HHV-6 的再激活与免疫功能低下患者的发病率有关，有时甚至导致死亡。迄今为止，人们对健康病毒携带者中病毒的控制以及疾病患者中病毒的失控仍知之甚少。特别是，对 HHV-6 特异性 T 细胞反应的了解有限。在这里，我们从健康供体的外周血单核细胞（PBMC）中描述了 HHV-6A 和 HHV-6B 特异性 CD4 和 CD8 T 细胞反应。我们研究了效应性 HHV-6 特异性 T 细胞的表型，以及与人类巨细胞病毒（HCMV）反应相比，刺激后诱导的特异性抑制性调节性 CD4 T 细胞。与 HCMV 相比，我们发现外周血中的 T 细胞反应可检测到，但频率非常低，对于 HHV-6A 和 -6B 病毒均如此。有趣的是，病毒之间特异性 T 细胞的表型也不同。HHV-6A 和 HHV-6B 特异性 CD4 T 淋巴细胞比 HCMV 特异性 T 细胞分化程度低。此外，我们发现与 HCMV 特异性 eTreg 相比，在合并感染个体中，HHV-6 特异性抑制性调节性 T 细胞（eTreg）的频率更高。尽管从病毒学角度来看，HHV-6 和 HCMV 非常相似，但我们观察到免疫上的差异，特别是与效应记忆和调节性病毒特异性 T 细胞的频率和表型有关。这表明在控制 HHV-6 感染时，与控制 HCMV 感染时相比，会募集不同的免疫因子。T 细胞是控制持续性病毒感染的核心，这些病毒可以与人类巨细胞病毒（HCMV）或人类疱疹病毒 6（HHV-6）有关。然而，对 HHV-6 特异性 T 细胞反应的了解有限。为了更深入地了解针对 HHV-6 的 T 细胞反应，我们直接从健康合并感染的献血者中描述了 HHV-6A 和 HHV-6B 特异性 CD4 和 CD8 T 细胞反应。尽管从病毒学角度来看，HHV-6 和 HCMV 非常相似，但我们观察到免疫上的差异，特别是与效应记忆和调节性病毒特异性 T 细胞的频率和表型有关。这表明在控制 HHV-6 感染时，与控制 HCMV 感染时相比，会募集不同的免疫因子。我们的发现可能会鼓励对病毒复制发作患者进行免疫监测，以跟踪效应性与调节性 T 细胞的出现。
