Abstract |
Protection against influenza is mediated by neutralizing antibodies, and their induction at high and sustained titers is key for successful vaccination. Optimal B cells activation requires delivery of help from CD4(+) T lymphocytes. In lymph nodes and tonsils, T-follicular helper cells have been identified as the T cells subset specialized in helping B lymphocytes, with interleukin-21 (IL-21) and inducible costimulatory molecule (ICOS1) playing a central role for this function. We followed the expansion of antigen-specific IL-21(+) CD4(+) T cells upon influenza vaccination in adults. We show that, after an overnight in vitro stimulation, influenza-specific IL-21(+) CD4(+) T cells can be measured in human blood, accumulate in the CXCR5(-)ICOS1(+) population, and increase in frequency after vaccination. The expansion of influenza-specific ICOS1(+)IL-21(+) CD4(+) T cells associates with and predicts the rise of functionally active antibodies to avian H5N1. We also show that blood-derived CXCR5(-)ICOS1(+) CD4(+) T cells exert helper function in vitro and support the differentiation of influenza specific B cells in an ICOS1- and IL-21-dependent manner. We propose that the expansion of antigen-specific ICOS1(+)IL-21(+) CD4(+) T cells in blood is an early marker of vaccine immunogenicity and an important immune parameter for the evaluation of novel vaccination strategies.
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Authors | Fabiana Spensieri, Erica Borgogni, Luisanna Zedda, Monia Bardelli, Francesca Buricchi, Gianfranco Volpini, Elena Fragapane, Simona Tavarini, Oretta Finco, Rino Rappuoli, Giuseppe Del Giudice, Grazia Galli, Flora Castellino |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 110
Issue 35
Pg. 14330-5
(Aug 27 2013)
ISSN: 1091-6490 [Electronic] United States |
PMID | 23940329
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Viral
- Influenza Vaccines
- Interleukins
- interleukin-21
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Topics |
- Antibodies, Viral
(blood, immunology)
- CD4-Positive T-Lymphocytes
(immunology)
- Humans
- Influenza A virus
(immunology)
- Influenza Vaccines
(administration & dosage, immunology)
- Influenza, Human
(blood, immunology, prevention & control)
- Interleukins
- Vaccination
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