Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Academic Article uri icon

Overview

MeSH

  • Cell Differentiation
  • Cell Movement
  • Chemokine CXCL13
  • Gene Expression Profiling
  • Humans
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukins
  • Macrophage-Activating Factors
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Repressor Proteins
  • Signaling Lymphocytic Activation Molecule Family
  • Synovial Fluid

MeSH Major

  • Arthritis, Rheumatoid
  • B-Lymphocytes
  • T-Lymphocytes, Helper-Inducer

abstract

  • CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis. However, these cells are not exhausted, despite high PD-1 expression. Rather, using multidimensional cytometry, transcriptomics, and functional assays, we define a population of PD-1(hi)CXCR5(-) 'peripheral helper' T (TPH) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1(hi)CXCR5(+) T follicular helper cells, TPH cells induce plasma cell differentiation in vitro through IL-21 secretion and SLAMF5 interaction (refs 3, 4). However, global transcriptomics highlight differences between TPH cells and T follicular helper cells, including altered expression of BCL6 and BLIMP1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in TPH cells. TPH cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.

authors

publication date

  • February 1, 2017

has subject area

  • Arthritis, Rheumatoid
  • B-Lymphocytes
  • Cell Differentiation
  • Cell Movement
  • Chemokine CXCL13
  • Gene Expression Profiling
  • Humans
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukins
  • Macrophage-Activating Factors
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Repressor Proteins
  • Signaling Lymphocytic Activation Molecule Family
  • Synovial Fluid
  • T-Lymphocytes, Helper-Inducer

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5349321

Digital Object Identifier (DOI)

  • 10.1038/nature20810

PubMed ID

  • 28150777

Additional Document Info

start page

  • 110

end page

  • 114

volume

  • 542

number

  • 7639