Clonal expansion of mycobacterial heat-shock protein-reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients

Arthritis Rheum. 1997 Mar;40(3):510-9. doi: 10.1002/art.1780400317.

Abstract

Objective: To examine the reactivity pattern and T cell receptor (TCR) characteristics of mycobacterial heat-shock protein 65 (hsp65)-reactive T cells generated from paired synovial fluid (SF) and peripheral blood (PB) samples obtained from rheumatoid arthritis (RA) patients and from healthy subjects.

Methods: The reactivity pattern of hsp65-reactive T cell clones generated under limiting-dilution conditions was analyzed in 3H-thymidine incorporation assays. The TCR variable regions of these hsp65-reactive T cells were characterized by polymerase chain reaction with TCR AV- and BV-specific primers and by DNA sequence analysis of the third complementarity-determining region (CDR3).

Results: The hsp65-reactive T cells derived both from RA patients and controls preferentially recognized the 1-170 and 303-540 regions of hsp65 and did not cross-react with human hsp60. The hsp65-reactive T cell clones derived from RA patients displayed a restricted TCR AV and BV gene usage, which can be attributed to the limited clonal origin(s) of the independent T cell clones, as evidenced by CDR3 sequence analysis. These clonally expanded T cells were found in both PB and SF and in different inflamed joints of RA patients.

Conclusion: Our study suggests that there is in vivo clonal activation and expansion of mycobacterial hsp65-reactive T cells in patients with RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / analysis
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / pathology*
  • Bacterial Proteins / analysis
  • Chaperonin 60
  • Chaperonins / analysis
  • Chaperonins / chemistry
  • Clone Cells / chemistry
  • Clone Cells / physiology
  • Humans
  • Knee Joint / cytology
  • Peptide Fragments / physiology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Sequence Analysis, DNA
  • Synovial Fluid / cytology
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / cytology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Chaperonin 60
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • heat-shock protein 65, Mycobacterium
  • Chaperonins