title: ICOS(+)PD-1(+)CXCR3(+) T follicular helper cells contribute to the generation of high-avidity antibodies following influenza vaccination.
abstract: The immune mechanism leading to the generation of protective antibody responses following influenza trivalent inactivated vaccine (TIV) vaccinations remains largely uncharacterized. We recently reported that TIV vaccination induced a transient increase of circulating ICOS(+)PD-1(+)CXCR3(+) T follicular helper (cTfh) cells in blood, which positively correlated with the induction of protective antibody responses measured at day 28. However, whether and how these T cells directly contribute to antibody response remains unclear. In this study, we analyzed the changes after TIV vaccination in the amount and the avidity of the polyclonal antibodies specific for the HA1 subunit of the pandemic H1N1 virus, and analyzed the correlation with the increase of ICOS(+)PD-1(+)CXCR3(+) cTfh cells. We found that both the amount and the avidity of specific antibodies rapidly increased during the first 7 days after TIV. Importantly, the increase of ICOS(+)PD-1(+)CXCR3(+) cTfh cells strongly correlated with the increase in the avidity of antibodies, particularly in subjects who did not have high affinity antibodies at baseline. We propose that ICOS(+)PD-1(+)CXCR3(+) Tfh cells directly contribute to the generation of high-avidity antibodies after TIV vaccinations by selectively interacting with high affinity B cells at extrafollicular sites.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75204, USA.
authors.forename: Salah-Eddine
authors.initials: SE
authors.lastname: Bentebibel
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Surender
authors.initials: S
authors.lastname: Khurana
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75204, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmitt
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75204, USA.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Kurup
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75204, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75204, USA.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Obermoser
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75204, USA.
authors.forename: A Karolina
authors.initials: AK
authors.lastname: Palucka
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Sastre
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75204, USA.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; C515187:CXCR3 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D007252:Influenza Vaccines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054367:Receptors, CXCR3