Activation and Induction of Antigen-Specific T Follicular Helper Cells Play a Critical Role in Live-Attenuated Influenza Vaccine-Induced Human Mucosal Anti-influenza Antibody Response.
Activation and Induction of Antigen-Specific T Follicular Helper Cells Play a Critical Role in Live-Attenuated Influenza Vaccine-Induced Human Mucosal Anti-influenza Antibody Response.
复制标题
DOI：
10.1128/jvi.00114-18
复制
发表时间：
2018-06-01
影响因子：
5.4
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Aljurayyan A;Puksuriwong S;Ahmed M;Sharma R;Krishnan M;Sood S;Davies K;Rajashekar D;Leong S;McNamara PS;Gordon S;Zhang Q
最近，人们对研制鼻内预防呼吸道感染的疫苗越来越感兴趣。抗体应答对于疫苗诱导的保护至关重要，T滤泡辅助细胞（TFH）被认为是介导抗体应答的重要细胞。大多数支持TFH在抗体反应中的作用的数据来自动物研究，除了血液中存在TFH样细胞外，来自人类的直接证据有限。我们研究了TFH的激活和诱导及其在人鼻咽相关淋巴组织（NALT）中由减毒流感活疫苗（LAIV）诱导的抗流感抗体应答中的作用。流式细胞术分析TFH在腺扁桃体组织中的激活情况，并检测LAIV刺激扁桃体单核细胞（MNC）后的抗血凝素（anti-HA）抗体。通过流式细胞术分析诱导的TFH和CD154表达，研究了LAIV诱导抗原特异性TFH的作用。LAIV诱导TFH增殖，这与抗ha抗体的产生相关，TFH被证明是抗体反应的关键。LAIV诱导初始T细胞的TFH表达BCL6和CD21，随后检测到抗ha抗体。laiv诱导的TFH抗原特异性通过在H1N1病毒抗原或HA攻击下表达抗原特异性T细胞活化标记CD154得到证实。laiv诱导的TFH分化被BCL6、白介素-21 （IL-21）、ICOS和CD40信号阻断所抑制，并减少抗ha抗体的产生。总之，我们证明了LAIV在人NALT中诱导抗原特异性TFH，这为抗流感抗体反应提供了关键支持。通过使用鼻内疫苗促进NALT中抗原特异性TFH可能为预防人类呼吸道感染提供一种有效的疫苗接种策略。重要性：呼吸道感染，如流感，在人类中很常见。鼻内疫苗接种被认为是一种具有生物学意义的有效的预防呼吸道感染的免疫方法。疫苗诱导的抗体反应对于预防感染至关重要。最近来自动物研究的数据表明，一种类型的T细胞TFH对抗体反应很重要。然而，由于缺乏对含有TFH的人体免疫组织的接触，关于TFH介导的抗体产生是否在人体中起作用的数据有限。在这项研究中，我们证明了TFH在人免疫组织中的诱导作用，通过使用鼻内流感疫苗为抗流感抗体反应提供了关键支持。我们的研究结果提供了直接证据，证明TFH在人类疫苗诱导的免疫中起着关键作用，并提出了一种通过使用鼻内疫苗来促进这种细胞抵抗呼吸道感染的新策略。
There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. The antibody response is critical for vaccine-induced protection, and T follicular helper cells (TFH) are considered important for mediating the antibody response. Most data supporting the role for TFH in the antibody response are from animal studies, and direct evidence from humans is limited, apart from the presence of TFH-like cells in blood. We studied the activation and induction of TFH and their role in the anti-influenza antibody response induced by a live-attenuated influenza vaccine (LAIV) in human nasopharynx-associated lymphoid tissue (NALT). TFH activation in adenotonsillar tissues was analyzed by flow cytometry, and anti-hemagglutinin (anti-HA) antibodies were examined following LAIV stimulation of tonsillar mononuclear cells (MNC). Induction of antigen-specific TFH by LAIV was studied by flow cytometry analysis of induced TFH and CD154 expression. LAIV induced TFH proliferation, which correlated with anti-HA antibody production, and TFH were shown to be critical for the antibody response. Induction of TFH from naive T cells by LAIV was shown in newly induced TFH expressing BCL6 and CD21, followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced TFH was demonstrated by expression of the antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced TFH differentiation was inhibited by BCL6, interleukin-21 (IL-21), ICOS, and CD40 signaling blocking, and that diminished anti-HA antibody production. In conclusion, we demonstrated the induction by LAIV of antigen-specific TFH in human NALT that provide critical support for the anti-influenza antibody response. Promoting antigen-specific TFH in NALT by use of intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans. IMPORTANCE Airway infections, such as influenza, are common in humans. Intranasal vaccination has been considered a biologically relevant and effective way of immunization against airway infection. The vaccine-induced antibody response is crucial for protection against infection. Recent data from animal studies suggest that one type of T cells, TFH, are important for the antibody response. However, data on whether TFH-mediated help for antibody production operates in humans are limited due to the lack of access to human immune tissue containing TFH. In this study, we demonstrate the induction of TFH in human immune tissue, providing critical support for the anti-influenza antibody response, by use of an intranasal influenza vaccine. Our findings provide direct evidence that TFH play a critical role in vaccine-induced immunity in humans and suggest a novel strategy for promoting such cells by use of intranasal vaccines against respiratory infections.