Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination.
Document Type
Article
Publication Date
3-13-2013
Keywords
Adult, Antibody Formation, Antigens, Viral, CD4-Positive T-Lymphocytes, CD40 Ligand, Cells, Cultured, Child, Cytokines, Female, Flow Cytometry, Humans, Influenza Vaccines, Male, Receptors, CXCR3, Receptors, CXCR5, T-Lymphocytes, Helper-Inducer
JAX Source
Sci Transl Med 2013 Apr 17; 5(176):176ra32
Volume
5
Issue
176
First Page
176
Last Page
176
ISSN
1946-6242
PMID
23486778
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. Sci Transl Med 2013 Apr 17; 5(176):176ra32
Recommended Citation
Bentebibel S,
Lopez S,
Obermoser G,
Schmitt N,
Mueller C,
Harrod C,
Flano E,
Mejias A,
Albrecht R,
Blankenship D,
Xu H,
Pascual V,
Banchereau J,
Garcia-Sastre A,
Palucka A,
Ramilo O,
Ueno H.
Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Sci Transl Med 2013 Apr 17; 5(176):176ra32