Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis.

By Michael Thomas Wong, Jinmiao Chen, Sriram Narayanan, Wenyu Lin, Rosslyn Anicete, Henry Tan Kun Kiaang, M. A. D. de Lafaille, Michael Poidinger, Evan W. Newell. 2015

121 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology

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Citations in the corpus

Automated optimized parameters for T-distributed stochastic neighbor embedding improve visualization and analysis of large datasets (2019, methodology): “In addition, t-SNE maps are used to categorize single cell data into relevant biological populations for downstream quanti ﬁ cation, achievable through expert-guided ﬁ ltering (gating) 4 or unsupervised clustering of the map 5 – 7 .”
Cytofkit: A Bioconductor Package for an Integrated Mass Cytometry Data Analysis Pipeline (2016, methodology): “Populations of naïve (CD45RACCR7 CD45RO), TH1 (IFN-γ ), TH17 (IL-17A ) and TFH (CXCR5 PD-1) cells are manually gated from the CD4 T cell dataset (see in [17]).”