TCRB clonotypes are present in CD4+ T cell populations prepared directly from rheumatoid synovium

Hum Immunol. 1997 Jun;55(1):11-21. doi: 10.1016/s0198-8859(97)00087-6.


The identification of clonal T cells at sites of inflammation is hampered by the large number of polyclonal T cells that nonspecifically accumulate. In this report, we combine the use of T cell sorting with spectratyping of the third complementarity determining region (CDR3) and direct sequence analysis to rapidly screen for and identify clonal expansions of T cells from synovial tissue specimens from patients with rheumatoid arthritis (RA). Initially, we used a polymerase chain reaction specific for the variable region gene of the T cell receptor beta chain (TCRBV) to compare the TCRBV repertoire expressed by CD4+ T cells from the peripheral blood and synovium of five patients with long-standing RA. Each patient had several TCRBV genes that were amplified to a greater degree from synovium. Extensive sequence analysis (n > 170) showed that each patient contained junctional sequences that occurred more than once, implying the presence of T cell clones within the starting CD4+ T cell population. To assess a more straightforward approach to identifying clones, six additional patients were recruited and CD4+, TCRBV2+ synovial T cells were positively selected and analyzed by CDR3 spectratyping. Bands deviating from a normal distribution were excised from the gel and sequenced directly. Clones were detected in half of the patients. These data are consistent with the possibility of an antigen-driven T cell response in RA that remains present in the setting of advanced disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology
  • Chromatography, High Pressure Liquid
  • Clone Cells
  • Gene Expression
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / immunology
  • Humans
  • Receptors, Antigen, T-Cell, alpha-beta / analysis*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Sequence Analysis, DNA
  • Synovial Membrane / immunology*
  • Synovial Membrane / pathology


  • Receptors, Antigen, T-Cell, alpha-beta