Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8+ T-Cell Profiles
Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8+ T-Cell Profiles
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DOI：
10.1164/rccm.201903-0588oc
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发表时间：
2020-02-01
影响因子：
24.7
通讯作者：
Cormier, Stephania A.
中科院分区：
文献类型：
--
作者：
Siefker, David T.;Luan Vu;Cormier, Stephania A.
原理：呼吸道合胞病毒（RSV）在全球范围内导致婴儿的严重发病率和死亡率。虽然辅助性T细胞2型（Th 2）细胞的病理是牵连在严重的疾病，免疫病理学的发展的机制是不完全understood.Objectives：我们的目的是确定与严重的RSV在婴儿的局部免疫反应。我们的假设是，疾病的严重程度将与增强的Th 2细胞responses.Methods：鼻吸出物收集严重（入住儿科ICU）或中度（维持在普通病房）RSV疾病住院的婴儿在5至9天后登记。通过评估T淋巴细胞的细胞结构，细胞因子浓度，和病毒load. Measures和主要结果的免疫反应进行了研究：严重疾病患者的CD 8（分化簇8）阳性T细胞表达IL-4（Tc 2）的比例增加和CD 8（+）T细胞表达IFN-γ（Tc 1）的比例减少。来自患有严重疾病的患者的鼻吸出物具有降低的IL-17浓度。Tc 1、表达IL-17（Tc 17）的CD 8（+）T细胞和表达IL-17（Th 17）的CD 4（+）T细胞频率较高的患者住院时间较短。Tc 1、Tc 17和Th 17与较短的住院时间相关，并可能发挥保护作用，而Tc 2细胞可能在病理学中发挥以前未被充分认识的作用。
Rationale: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Although T-helper type 2 (Th2) cell pathology is implicated in severe disease, the mechanisms underlying the development of immunopathology are incompletely understood.Objectives: We aimed to identify local immune responses associated with severe RSV in infants. Our hypothesis was that disease severity would correlate with enhanced Th2 cellular responses.Methods: Nasal aspirates were collected from infants hospitalized with severe (admitted to the pediatric ICU) or moderate (maintained in the general ward) RSV disease at 5 to 9 days after enrollment. The immune response was investigated by evaluating T-lymphocyte cellularity, cytokine concentration, and viral load.Measurements and Main Results: Patients with severe disease had increased proportions of CD8 (cluster of differentiation 8)positive T cells expressing IL-4 (Tc2) and reduced proportions of CD8(+) T cells expressing IFN-gamma (Tc1). Nasal aspirates from patients with severe disease had reduced concentrations of IL-17. Patients with greater frequencies of Tc1, CD8(+) T cells expressing IL-17 (Tc17), and CD4(+) T cells expressing IL-17 (Th17) had shorter durations of hospitalization.Conclusions: Severe RSV disease was associated with distinct T-cell profiles. Tc1, Tc17, and Th17 were associated with shorter hospital stay and may play a protective role, whereas Tc2 cells may play a previously underappreciated role in pathology.