Tweet
Sci Transl Med 13 March 2013:
Vol. 5, Issue 176, p. 176ra32
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3005191
Research Article
Influenza
Induction of ICOS+CXCR3+CXCR5+ TH Cells Correlates with Antibody Responses to Influenza Vaccination
Salah-Eddine Bentebibel1,2,*,
Santiago Lopez3,*,
Gerlinde Obermoser1,*,
Nathalie Schmitt1,*,
Cynthia Mueller1,
Carson Harrod1,2,
Emilio Flano3,
Asuncion Mejias3,
Randy A. Albrecht4,5,
Derek Blankenship1,
Hui Xu1,
Virginia Pascual1,2,
Jacques Banchereau1,
Adolfo Garcia-Sastre4,5,6,
Anna Karolina Palucka1,2,
Octavio Ramilo3,? and
Hideki Ueno1,2,?
+ Author Affiliations
1Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
2Institute of Biomedical Studies, Baylor University, Waco, TX 76798, USA.
3The Research Institute at Nationwide Children?s Hospital, Columbus, OH 43205, USA.
4Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
5Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
6Division of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
+ Author Notes
↵* These authors contributed equally to this work.
↵?Corresponding author. E-mail: Octavio.Ramilo@nationwidechildrens.org (O.R.); hidekiu@baylorhealth.edu (H.U.)
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 na?ve 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.
Vol. 5, Issue 176, p. 176ra32
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3005191
Research Article
Influenza
Induction of ICOS+CXCR3+CXCR5+ TH Cells Correlates with Antibody Responses to Influenza Vaccination
Salah-Eddine Bentebibel1,2,*,
Santiago Lopez3,*,
Gerlinde Obermoser1,*,
Nathalie Schmitt1,*,
Cynthia Mueller1,
Carson Harrod1,2,
Emilio Flano3,
Asuncion Mejias3,
Randy A. Albrecht4,5,
Derek Blankenship1,
Hui Xu1,
Virginia Pascual1,2,
Jacques Banchereau1,
Adolfo Garcia-Sastre4,5,6,
Anna Karolina Palucka1,2,
Octavio Ramilo3,? and
Hideki Ueno1,2,?
+ Author Affiliations
1Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
2Institute of Biomedical Studies, Baylor University, Waco, TX 76798, USA.
3The Research Institute at Nationwide Children?s Hospital, Columbus, OH 43205, USA.
4Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
5Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
6Division of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
+ Author Notes
↵* These authors contributed equally to this work.
↵?Corresponding author. E-mail: Octavio.Ramilo@nationwidechildrens.org (O.R.); hidekiu@baylorhealth.edu (H.U.)
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 na?ve 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.
