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Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis
- Source :
- Nature. 542(7639)
- Publication Year :
- 2016
-
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-1hiCXCR5-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-1hiCXCR5- 'peripheral helper' T (TPH) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1hiCXCR5+ 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.
- Subjects :
- 0301 basic medicine
Receptors, CXCR5
Programmed Cell Death 1 Receptor
Article
Arthritis, Rheumatoid
Inducible T-Cell Co-Stimulator Protein
03 medical and health sciences
Interleukin 21
0302 clinical medicine
Cell Movement
Signaling Lymphocytic Activation Molecule Family
Synovial Fluid
medicine
Cytotoxic T cell
Humans
IL-2 receptor
Antigen-presenting cell
030203 arthritis & rheumatology
B-Lymphocytes
Multidisciplinary
CD40
biology
Gene Expression Profiling
Interleukins
Cell Differentiation
T helper cell
T-Lymphocytes, Helper-Inducer
Natural killer T cell
Chemokine CXCL13
Repressor Proteins
030104 developmental biology
medicine.anatomical_structure
Macrophage-Activating Factors
Immunology
biology.protein
Interleukin 12
Proto-Oncogene Proteins c-bcl-6
Receptors, Chemokine
Positive Regulatory Domain I-Binding Factor 1
Subjects
Details
- ISSN :
- 14764687
- Volume :
- 542
- Issue :
- 7639
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....45857bb84471efb8b7aa229cead7def0