Activated T follicular helper-like cells are released into blood after oral vaccination and correlate with vaccine specific mucosal B-cell memory
Activated T follicular helper-like cells are released into blood after oral vaccination and correlate with vaccine specific mucosal B-cell memory
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DOI：
10.1038/s41598-018-20740-3
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发表时间：
2018-02-09
影响因子：
4.6
通讯作者：
Lundgren, Anna
中科院分区：
文献类型：
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作者：
Cardeno, Ana;Magnusson, Maria K.;Lundgren, Anna
T滤泡辅助细胞(TFH)样细胞具有强大的B细胞帮助能力，在非肠道接种后被动员到人体循环中，通常被认为反映了正在进行的生发中心反应。然而，黏膜疫苗接种是否诱导全身性TFH反应以及这种反应可能如何与IgA的产生有关尚不清楚。我们研究了口服产肠毒素大肠杆菌灭活疫苗成人外周血中类Tfh细胞的频率、表型和功能。根据受试者对主要疫苗抗原的肠道抗体分泌细胞(ASC)IgA反应，将受试者分为疫苗应答者或弱应答者/无应答者。口服免疫可显著增加ASC应答者cTfh细胞表达cTfh激活标志物可诱导共刺激分子(ICOS)的比例，但对弱/无应答者无明显影响。疫苗接种还通过激活cTfh细胞增强IL-21、Th17标志物和整合素β7的表达，支持功能和肠道归巢潜能。CTfh细胞可促进共培养的B细胞产生总IgA和疫苗特异性IgA。初次接种后一周内评估的cTfh反应的大小与1-2年后记忆肠源性疫苗特异性IgA反应相关。我们的结论是，口服疫苗后，激活的ICOS+Tfh样细胞被动员到血液中，可以作为人类疫苗特异性粘膜记忆的生物标志物。
T follicular helper (Tfh)-like cells with potent B-cell helping ability are mobilized into human circulation after parenteral vaccination and are generally held to reflect ongoing germinal center reactions. However, whether mucosal vaccination induces systemic Tfh responses and how such responses may relate to IgA production are unknown. We investigated the frequencies, phenotype and function of circulating Tfh-like CD4(+) CXCR5(+) T cells (cTfh) in adults receiving an oral inactivated enterotoxigenic Escherichia coli vaccine. Subjects were classified as vaccine responders or weak/non-responders based on their intestine-derived antibody-secreting cell (ASC) IgA responses to major vaccine antigens. Oral immunization induced significantly increased proportions of cTfh cells expressing the cTfh activation marker inducible costimulator (ICOS) in ASC responders, but not in weak/non-responders. Vaccination also enhanced the expression of IL-21, Th17 markers and integrin beta 7 by activated cTfh cells, supporting functionality and gut homing potential. cTfh cells promoted total and vaccine specific IgA production from cocultured B cells. Magnitudes of cTfh responses assessed within a week after primary vaccinations correlated with memory intestine-derived vaccine specific IgA responses 1-2 years later. We conclude that activated ICOS+ Tfh-like cells are mobilized into blood after oral vaccination and may be used as biomarkers of vaccine specific mucosal memory in humans.