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

Cell Rep. 2015 Jun 23;11(11):1822-33. doi: 10.1016/j.celrep.2015.05.022. Epub 2015 Jun 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Palatine Tonsil / cytology*
  • Palatine Tonsil / growth & development
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / metabolism
  • T-Lymphocytes, Helper-Inducer / classification
  • T-Lymphocytes, Helper-Inducer / metabolism*


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Programmed Cell Death 1 Receptor
  • Receptors, CCR7
  • Receptors, CXCR5
  • Interferon-gamma