Inflamed target tissue provides a specific niche for highly expanded T-cell clones in early human autoimmune disease

Ann Rheum Dis. 2012 Jun;71(6):1088-93. doi: 10.1136/annrheumdis-2011-200612. Epub 2012 Jan 31.


Objective: To profile quantitatively the T-cell repertoire in multiple joints and peripheral blood of patients with recent onset (early) or established rheumatoid arthritis (RA) using a novel next-generation sequencing protocol to identify potential autoreactive clones.

Methods: Synovium of patients with recent onset (early) RA (<6 months) (n=6) or established RA (>18 months) (n=6) was screened for T-cell clones by sequencing over 10 000 T-cell receptors (TCR) per sample. T cells from paired blood samples were analysed for comparison. From two patients synovial T cells were obtained from multiple inflamed joints. The degree of expansion of each individual clone was based on its unique CDR3 sequence frequency within a sample. Clones with a frequency of over 0.5% were considered to be highly expanded clones (HEC).

Results: In early RA synovium, the T-cell repertoire was dominated by 35 HEC (median, range 2-70) accounting for 56% of the TCR sequenced. The clonal dominance in the synovium was patient specific and significantly greater than in established RA (median of 11 HEC (range 5-24) in established RA synovium accounting for 9.8% of T cells; p<0.01). 34% (range 28-40%) of the most expanded T-cell clones were shared between different joints in the same patients, compared with only 4% (range 0-8%) between synovium and blood (p=0.01).

Conclusions: In RA, a systemic autoimmune disease, the inflamed synovium forms a niche for specific expanded T-cell clones, especially in early disease. This suggests that, at least in RA, autoreactive T cells should be addressed specifically in the inflamed tissue, preferably in the early phase of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology*
  • Autoimmunity / immunology*
  • Biopsy
  • Cellular Microenvironment / immunology
  • Clone Cells / cytology
  • Clone Cells / immunology
  • Disease Progression
  • Humans
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*