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Activated T follicular helper-like cells are released into blood after oral vaccination and correlate with vaccine specific mucosal B-cell memory

Journal article
Authors Ana Cardeno
Maria K Magnusson
Marianne Quiding-Järbrink
Anna Lundgren
Published in Scientific Reports
Volume 8
ISSN 2045-2322
Publication year 2018
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Links dx.doi.org/10.1038/s41598-018-20740...
Keywords enterotoxigenic escherichia-coli, intestinal immune-responses, antibody-responses, tfh cells, immunological memory, elispot assays, dmlt adjuvant, etec vaccine, humans, antigen, Science & Technology - Other Topics
Subject categories Medical microbiology

Abstract

T follicular helper (Tfh)-like cells with potent B-cell helping ability are mobilized into human circulation after parenteral vaccination and are generally held to reflect ongoing germinal center reactions. However, whether mucosal vaccination induces systemic Tfh responses and how such responses may relate to IgA production are unknown. We investigated the frequencies, phenotype and function of circulating Tfh-like CD4(+) CXCR5(+) T cells (cTfh) in adults receiving an oral inactivated enterotoxigenic Escherichia coli vaccine. Subjects were classified as vaccine responders or weak/non-responders based on their intestine-derived antibody-secreting cell (ASC) IgA responses to major vaccine antigens. Oral immunization induced significantly increased proportions of cTfh cells expressing the cTfh activation marker inducible costimulator (ICOS) in ASC responders, but not in weak/non-responders. Vaccination also enhanced the expression of IL-21, Th17 markers and integrin beta 7 by activated cTfh cells, supporting functionality and gut homing potential. cTfh cells promoted total and vaccine specific IgA production from cocultured B cells. Magnitudes of cTfh responses assessed within a week after primary vaccinations correlated with memory intestine-derived vaccine specific IgA responses 1-2 years later. We conclude that activated ICOS+ Tfh-like cells are mobilized into blood after oral vaccination and may be used as biomarkers of vaccine specific mucosal memory in humans.

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