title: Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination.
abstract: Seasonal influenza vaccine protects 60 to 90% of healthy young adults from influenza infection. The immunological events that lead to the induction of protective antibody responses remain poorly understood in humans. We identified the type of CD4+ T cells associated with protective antibody responses after seasonal influenza vaccinations. The administration of trivalent split-virus influenza vaccines induced a temporary increase of CD4+ T cells expressing ICOS, which peaked at day 7, as did plasmablasts. The induction of ICOS was largely restricted to CD4+ T cells coexpressing the chemokine receptors CXCR3 and CXCR5, a subpopulation of circulating memory T follicular helper cells. Up to 60% of these ICOS+CXCR3+CXCR5+CD4+ T cells were specific for influenza antigens and expressed interleukin-2 (IL-2), IL-10, IL-21, and interferon-γ upon antigen stimulation. The increase of ICOS+CXCR3+CXCR5+CD4+ T cells in blood correlated with the increase of preexisting antibody titers, but not with the induction of primary antibody responses. Consistently, purified ICOS+CXCR3+CXCR5+CD4+ T cells efficiently induced memory B cells, but not naïve B cells, to differentiate into plasma cells that produce influenza-specific antibodies ex vivo. Thus, the emergence of blood ICOS+CXCR3+CXCR5+CD4+ T cells correlates with the development of protective antibody responses generated by memory B cells upon seasonal influenza vaccination.
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.forename: Santiago
authors.initials: S
authors.lastname: Lopez
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Obermoser
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmitt
authors.forename: Cynthia
authors.initials: C
authors.lastname: Mueller
authors.forename: Carson
authors.initials: C
authors.lastname: Harrod
authors.forename: Emilio
authors.initials: E
authors.lastname: Flano
authors.forename: Asuncion
authors.initials: A
authors.lastname: Mejias
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.forename: Derek
authors.initials: D
authors.lastname: Blankenship
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Sastre
authors.forename: Anna Karolina
authors.initials: AK
authors.lastname: Palucka
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000328:Adult; D000917:Antibody Formation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D054367:Receptors, CXCR3 / Q000378:metabolism*; D054380:Receptors, CXCR5 / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; C515187:CXCR3 protein, human; C095085:CXCR5 protein, human; D016207:Cytokines; D007252:Influenza Vaccines; D054367:Receptors, CXCR3; D054380:Receptors, CXCR5; D023201:CD40 Ligand