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

Michael P. Davey, Gary A. Burgoine, Carolyn N. Woody

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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 β 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.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalHuman Immunology
Volume55
Issue number1
DOIs
StatePublished - Jun 1 1997

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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