Title

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

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