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Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-01-01 , DOI: 10.1093/infdis/jiz321
Sarah Lartey 1 , Fan Zhou 1, 2 , Karl A Brokstad 3 , Kristin G-I Mohn 1 , Steffen A Slettevoll 1 , Rishi D Pathirana 1 , Rebecca J Cox 1, 2, 4
Affiliation  

BACKGROUND Influenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown. METHODS We collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay. RESULTS We report that LAIV induced early (3-7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV. CONCLUSIONS Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.

中文翻译:

活接种的流感疫苗诱导与抗体诱导相关的扁桃体滤泡T辅助细胞反应。

背景技术流行性感冒仍然是对公共健康的主要威胁。减毒流感疫苗(LAIV)已被证明是有效的,特别是对于儿童。卵泡T辅助(TFH)细胞提供B细胞帮助,对于产生长期体液免疫至关重要。但是,TFH细胞在LAIV诱导的免疫反应中的作用尚不清楚。方法我们收集了扁桃体切除术前接受LAIV的儿童和成人的扁桃体,血浆和唾液样本。我们通过流式细胞仪和免疫组织化学测量了LAIV后的流感特异性TFH细胞应答。通过血凝抑制测定和酶联免疫吸附测定分析全身和局部抗体应答。结果我们报道了LAIV在儿童中诱导了扁桃体卵泡的早期激活(疫苗接种后3-7天)和流感特异性TFH细胞(CXCR5 + CD57 + CD4 + T细胞)的反应,而成年人的反应程度较小。血清学分析表明,LAIV引起儿童而非成年人的快速(接种后第14天)和长期(接种后长达1年)抗体应答(血凝抑制,流感特异性IgG)。预先存在的流感特异性唾液IgA浓度与扁桃体TFH细胞反应之间呈负相关,而LAIV后扁桃体TFH细胞与全身性IgG诱导之间呈正相关。结论我们的数据合在一起证明了扁桃体TFH细胞在LAIV诱导的人类免疫中的重要作用。血清学分析表明,LAIV引起儿童而非成年人的快速(接种后第14天)和长期(接种后长达1年)抗体应答(血凝抑制,流感特异性IgG)。预先存在的流感特异性唾液IgA浓度与扁桃体TFH细胞反应之间呈负相关,而LAIV后扁桃体TFH细胞与全身性IgG诱导之间呈正相关。结论我们的数据合在一起证明了扁桃体TFH细胞在LAIV诱导的人类免疫中的重要作用。血清学分析表明,LAIV引起儿童而非成年人的快速(接种后第14天)和长期(接种后长达1年)抗体应答(血凝抑制,流感特异性IgG)。预先存在的流感特异性唾液IgA浓度与扁桃体TFH细胞反应之间呈负相关,而LAIV后扁桃体TFH细胞与全身性IgG诱导之间呈正相关。结论我们的数据合在一起证明了扁桃体TFH细胞在LAIV诱导的人类免疫中的重要作用。预先存在的流感特异性唾液IgA浓度与扁桃体TFH细胞反应之间呈负相关,而LAIV后扁桃体TFH细胞与全身性IgG诱导之间呈正相关。结论我们的数据合在一起证明了扁桃体TFH细胞在LAIV诱导的人类免疫中的重要作用。预先存在的流感特异性唾液IgA浓度与扁桃体TFH细胞反应之间呈负相关,而LAIV后扁桃体TFH细胞与全身性IgG诱导之间呈正相关。结论我们的数据合在一起证明了扁桃体TFH细胞在LAIV诱导的人类免疫中的重要作用。
更新日期:2019-07-27
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