Induction of ICOS + CXCR3 + CXCR5 + T H Cells Correlates with Antibody Responses to Influenza Vaccination
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- 13 March 2013
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 5 (176), 176ra32
- https://doi.org/10.1126/scitranslmed.3005191
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.Keywords
This publication has 43 references indexed in Scilit:
- Follicular B helper T cell activity is confined to CXCR5hiICOShi CD4 T cells and is independent of CD57 expressionEuropean Journal of Immunology, 2006
- Influenza and the challenge for immunologyNature Immunology, 2006
- A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profilesNature Medicine, 2005
- The Role of ICOS in the CXCR5+ Follicular B Helper T Cell Maintenance In VivoThe Journal of Immunology, 2005
- T Follicular Helper Cells Express a Distinctive Transcriptional Profile, Reflecting Their Role as Non-Th1/Th2 Effector Cells That Provide Help for B CellsThe Journal of Immunology, 2004
- Extrafollicular antibody responsesImmunological Reviews, 2003
- Subspecialization of Cxcr5+ T CellsThe Journal of Experimental Medicine, 2001
- Follicular B Helper T Cells Express Cxc Chemokine Receptor 5, Localize to B Cell Follicles, and Support Immunoglobulin ProductionThe Journal of Experimental Medicine, 2000
- ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28Nature, 1999
- The Efficacy and Cost Effectiveness of Vaccination against Influenza among Elderly Persons Living in the CommunityThe New England Journal of Medicine, 1994