Biomaterial Database

Human circulating influenza-CD4+ ICOS1+IL-21+ T cells expand after vaccination, exert helper function, and predict antibody responses. 2013

Fabiana Spensieri, and Erica Borgogni, and Luisanna Zedda, and Monia Bardelli, and Francesca Buricchi, and Gianfranco Volpini, and Elena Fragapane, and Simona Tavarini, and Oretta Finco, and Rino Rappuoli, and Giuseppe Del Giudice, and Grazia Galli, and Flora Castellino

Research Center, Novartis Vaccines and Diagnostics, Srl, 53100 Siena, Italy.

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.

UI	MeSH Term	Description	Entries
D007251	Influenza, Human	An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia.	Grippe,Human Flu,Human Influenza,Influenza in Humans,Influenza,Flu, Human,Human Influenzas,Influenza in Human,Influenzas,Influenzas, Human
D007252	Influenza Vaccines	Vaccines used to prevent infection by viruses in the family ORTHOMYXOVIRIDAE. It includes both killed and attenuated vaccines. The composition of the vaccines is changed each year in response to antigenic shifts and changes in prevalence of influenza virus strains. The flu vaccines may be mono- or multi-valent, which contains one or more ALPHAINFLUENZAVIRUS and BETAINFLUENZAVIRUS strains.	Flu Vaccine,Influenzavirus Vaccine,Monovalent Influenza Vaccine,Universal Flu Vaccine,Universal Influenza Vaccine,Flu Vaccines,High-Dose Trivalent Influenza Vaccine,Influenza Vaccine,Influenza Virus Vaccine,Influenza Virus Vaccines,Influenzavirus Vaccines,Intranasal Live-Attenuated Influenza Vaccine,LAIV Vaccine,Monovalent Influenza Vaccines,Quadrivalent Influenza Vaccine,Trivalent Influenza Vaccine,Trivalent Live Attenuated Influenza Vaccine,Universal Flu Vaccines,Universal Influenza Vaccines,Flu Vaccine, Universal,High Dose Trivalent Influenza Vaccine,Influenza Vaccine, Monovalent,Influenza Vaccine, Quadrivalent,Influenza Vaccine, Trivalent,Influenza Vaccine, Universal,Intranasal Live Attenuated Influenza Vaccine,Vaccine, Flu,Vaccine, Influenza,Vaccine, Influenza Virus,Vaccine, Influenzavirus,Vaccine, LAIV,Vaccine, Monovalent Influenza,Vaccine, Quadrivalent Influenza,Vaccine, Trivalent Influenza,Virus Vaccine, Influenza
D007378	Interleukins	Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.	Interleukin
D009980	Influenza A virus	The type species of the genus ALPHAINFLUENZAVIRUS that causes influenza and other diseases in humans and animals. Antigenic variation occurs frequently between strains, allowing classification into subtypes and variants. Transmission is usually by aerosol (human and most non-aquatic hosts) or waterborne (ducks). Infected birds shed the virus in their saliva, nasal secretions, and feces.	Alphainfluenzavirus influenzae,Avian Orthomyxovirus Type A,FLUAV,Fowl Plague Virus,Human Influenza A Virus,Influenza Virus Type A,Influenza Viruses Type A,Myxovirus influenzae-A hominis,Myxovirus influenzae-A suis,Myxovirus pestis galli,Orthomyxovirus Type A,Orthomyxovirus Type A, Avian,Orthomyxovirus Type A, Human,Orthomyxovirus Type A, Porcine,Pestis galli Myxovirus,Fowl Plague Viruses,Influenza A viruses,Myxovirus influenzae A hominis,Myxovirus influenzae A suis,Myxovirus, Pestis galli,Myxoviruses, Pestis galli,Pestis galli Myxoviruses,Plague Virus, Fowl,Virus, Fowl Plague
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000914	Antibodies, Viral	Immunoglobulins produced in response to VIRAL ANTIGENS.	Viral Antibodies
D014611	Vaccination	Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.	Immunization, Active,Active Immunization,Active Immunizations,Immunizations, Active,Vaccinations
D015496	CD4-Positive T-Lymphocytes	A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.	T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte