Induction of ICOS+CXCR3+CXCR5+ T H cells correlates with antibody responses to influenza vaccination

Salah Eddine Bentebibel, Santiago Lopez, Gerlinde Obermoser, Nathalie Schmitt, Cynthia Mueller, Carson Harrod, Emilio Flano, Asuncion Mejias, Randy A. Albrecht, Derek Blankenship, Hui Xu, Virginia Pascual, Jacques Banchereau, Adolfo Garcia-Sastre, Anna Karolina Palucka, Octavio Ramilo, Hideki Ueno

Research output: Contribution to journalArticlepeer-review

457 Scopus citations


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.

Original languageEnglish (US)
Article number176ra32
JournalScience translational medicine
Issue number176
StatePublished - Mar 13 2013
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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