CD4+ T Follicular Helper Cells in Human Tonsils and Blood Are Clonally Convergent but Divergent from Non-Tfh CD4+ Cells
Elena Brenna,
Alexey N. Davydov,
Kristin Ladell,
James E. McLaren,
Paolo Bonaiuti,
Maria Metsger,
James D. Ramsden,
Sarah C. Gilbert,
Teresa Lambe,
David A. Price,
Suzanne L. Campion,
Dmitriy M. Chudakov,
Persephone Borrow,
Andrew J. McMichael
Affiliations
Elena Brenna
Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK; Corresponding author
Alexey N. Davydov
Central European Institute of Technology, Brno 601 77, Czech Republic
Kristin Ladell
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
James E. McLaren
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
Paolo Bonaiuti
Istituto Firc di Oncologia Molecolare, Milano 20139, Italy
Maria Metsger
Central European Institute of Technology, Brno 601 77, Czech Republic
James D. Ramsden
West Wing ENT, John Radcliffe Hospital, Oxford OX3 9DU, UK
Sarah C. Gilbert
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Teresa Lambe
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
David A. Price
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK; Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
Suzanne L. Campion
Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK
Dmitriy M. Chudakov
Central European Institute of Technology, Brno 601 77, Czech Republic; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow 117997, Russia
Persephone Borrow
Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK; Corresponding author
Andrew J. McMichael
Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK; Corresponding author
Summary: T follicular helper (Tfh) cells are fundamental for B cell selection and antibody maturation in germinal centers. Circulating Tfh (cTfh) cells constitute a minor proportion of the CD4+ T cells in peripheral blood, but their clonotypic relationship to Tfh populations resident in lymph nodes and the extent to which they differ from non-Tfh CD4+ cells have been unclear. Using donor-matched blood and tonsil samples, we investigate T cell receptor (TCR) sharing between tonsillar Tfh cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing reveals considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. Furthermore, influenza-specific cTfh cell clones derived from blood can be found in the repertoire of tonsillar Tfh cells. Therefore, human blood samples can be used to gain insight into the specificity of Tfh responses occurring in lymphoid tissues, provided that cTfh subsets are studied. : CD4+ T follicular helper (Tfh) cells are fundamental for antibody production. Brenna et al. demonstrate extensive repertoire overlap between Tfh populations in human blood and tonsils, whereas non-Tfh repertoires differ profoundly. Therefore, analysis of Tfh but not of total circulating CD4+ T cells can reflect the specificity of lymphoid tissue Tfh cells. Keywords: T follicular helper cells, TCR repertoire, influenza, tonsil, blood
