title: Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis.
abstract: Single-cell analysis technologies such as mass cytometry allow for measurements of cellular heterogeneity with unprecedented dimensionality. Here, we applied dimensionality reduction and automated clustering methods on human T helper (T(H)) cells derived from peripheral blood and tonsils, which showed differential cell composition and extensive T(H) cell heterogeneity. Notably, this analysis revealed numerous subtypes of follicular helper T (T(FH)) cells that followed a continuum spanning both blood and tonsils. Furthermore, we identified tonsillar CXCR5(lo)PD-1(lo)CCR7(lo) T(FH) cells expressing interferon-γ (IFN-γ), interleukin-17 (IL-17), or Foxp3, indicating that T(FH) cells exhibit diverse functional capacities within extrafollicular stages. Regression analysis demonstrated that CXCR5(lo)PD-1(-) and CXCR5(lo)PD-1(lo) cells accumulate during childhood in secondary lymphoid organs, supporting previous findings that these subsets represent memory T(FH) cells. This study provides an in-depth comparison of human blood and tonsillar T(FH) cells and outlines a general approach for subset discovery and hypothesizing of cellular progressions.
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wong
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors.forename: Jinmiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors.forename: Sriram
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Lin
authors.affiliation: KK Women's and Children's Hospital, Department of Otolaryngology, Singapore 229899, Singapore.
authors.forename: Rosslyn
authors.initials: R
authors.lastname: Anicete
authors.affiliation: KK Women's and Children's Hospital, Department of Otolaryngology, Singapore 229899, Singapore.
authors.forename: Henry Tan Kun
authors.initials: HT
authors.lastname: Kiaang
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors.forename: Maria Alicia Curotto
authors.initials: MA
authors.lastname: De Lafaille
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore. Electronic address: evan_newell@immunol.a-star.edu.sg.
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
mesh_terms: D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology* / Q000254:growth & development; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D061026:Programmed Cell Death 1 Receptor; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D007371:Interferon-gamma