{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:31:23Z","timestamp":1787016683824,"version":"build-2736575974"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T00:00:00Z","timestamp":1526256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Royal Embassy of Saudi Arabia Culture Bureau","award":["Studentship"],"award-info":[{"award-number":["Studentship"]}]},{"DOI":"10.13039\/501100000861","name":"Sparks","doi-asserted-by":"publisher","award":["15Liv01"],"award-info":[{"award-number":["15Liv01"]}],"id":[{"id":"10.13039\/501100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000374","name":"British Medical Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    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 (T\n                    <jats:sub>FH<\/jats:sub>\n                    ) are considered important for mediating the antibody response. Most data supporting the role for T\n                    <jats:sub>FH<\/jats:sub>\n                    in the antibody response are from animal studies, and direct evidence from humans is limited, apart from the presence of T\n                    <jats:sub>FH<\/jats:sub>\n                    -like cells in blood. We studied the activation and induction of T\n                    <jats:sub>FH<\/jats:sub>\n                    and their role in the anti-influenza antibody response induced by a live-attenuated influenza vaccine (LAIV) in human nasopharynx-associated lymphoid tissue (NALT). T\n                    <jats:sub>FH<\/jats:sub>\n                    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 T\n                    <jats:sub>FH<\/jats:sub>\n                    by LAIV was studied by flow cytometry analysis of induced T\n                    <jats:sub>FH<\/jats:sub>\n                    and CD154 expression. LAIV induced T\n                    <jats:sub>FH<\/jats:sub>\n                    proliferation, which correlated with anti-HA antibody production, and T\n                    <jats:sub>FH<\/jats:sub>\n                    were shown to be critical for the antibody response. Induction of T\n                    <jats:sub>FH<\/jats:sub>\n                    from naive T cells by LAIV was shown in newly induced T\n                    <jats:sub>FH<\/jats:sub>\n                    expressing BCL6 and CD21, followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced T\n                    <jats:sub>FH<\/jats:sub>\n                    was demonstrated by expression of the antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced T\n                    <jats:sub>FH<\/jats:sub>\n                    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 T\n                    <jats:sub>FH<\/jats:sub>\n                    in human NALT that provide critical support for the anti-influenza antibody response. Promoting antigen-specific T\n                    <jats:sub>FH<\/jats:sub>\n                    in NALT by use of intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    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, T\n                    <jats:sub>FH<\/jats:sub>\n                    , are important for the antibody response. However, data on whether T\n                    <jats:sub>FH<\/jats:sub>\n                    -mediated help for antibody production operates in humans are limited due to the lack of access to human immune tissue containing T\n                    <jats:sub>FH<\/jats:sub>\n                    . In this study, we demonstrate the induction of T\n                    <jats:sub>FH<\/jats:sub>\n                    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 T\n                    <jats:sub>FH<\/jats:sub>\n                    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.\n                  <\/jats:p>","DOI":"10.1128\/jvi.00114-18","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T08:49:11Z","timestamp":1521535751000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["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"],"prefix":"10.1128","volume":"92","author":[{"given":"Abdullah","family":"Aljurayyan","sequence":"first","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suttida","family":"Puksuriwong","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Sharma","sequence":"additional","affiliation":[{"name":"ENT Department, Alder Hey Children's Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhan","family":"Krishnan","sequence":"additional","affiliation":[{"name":"ENT Department, Alder Hey Children's Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salil","family":"Sood","sequence":"additional","affiliation":[{"name":"ENT Department, Alder Hey Children's Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Davies","sequence":"additional","affiliation":[{"name":"ENT Department, Royal Liverpool and Broadgreen University Hospitals, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Rajashekar","sequence":"additional","affiliation":[{"name":"ENT Department, Royal Liverpool and Broadgreen University Hospitals, Liverpool, United 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