title: A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA.
abstract: T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens.
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, United Kingdom; Immunology & HLA section, Pathology & Clinical Laboratory Medicine, King Fahad Medical City, Saudi Arabia.
authors.forename: A N
authors.initials: AN
authors.lastname: Aljurayyan
authors.affiliation: ENT Department, Alder Hey Children's Hospital, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.affiliation: ENT Department, Alder Hey Children's Hospital, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Upile
authors.affiliation: ENT Department, Alder Hey Children's Hospital, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Beer
authors.affiliation: ENT Department, Alder Hey Children's Hospital, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Vaughan
authors.affiliation: ENT Department, Alder Hey Children's Hospital, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Xie
authors.affiliation: ENT Department, Royal Liverpool and Broadgreen University Hospitals, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Achar
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: M S
authors.initials: MS
authors.lastname: Ahmed
authors.affiliation: Institute of Child Health, University of Liverpool, United Kingdom.
authors.forename: P S
authors.initials: PS
authors.lastname: McNamara
authors.affiliation: Liverpool School of Tropical Medicine, United Kingdom.
authors.forename: S B
authors.initials: SB
authors.lastname: Gordon
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, United Kingdom. Electronic address: qibo.zhang@liv.ac.uk.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D007223:Infant; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018655:Lymphocyte Count; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000941:Antigens; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009838:Oligodeoxyribonucleotides
keywords: Anti-hemagglutinin (HA) antibody response; Children and adults; CpG-DNA; Influenza vaccine; Influenza virus; Nasopharynx-associated lymphoid tissues (NALT); T follicular helper cell (T(FH))