Oligoclonal T cell proliferation in patients with rheumatoid arthritis and their unaffected siblings

Arthritis Rheum. 1996 Jun;39(6):904-13. doi: 10.1002/art.1780390606.


Objective: To analyze whether patients with rheumatoid arthritis (RA) have an intrinsic defect in T cell proliferation and survival, possibly contributing to the infiltration of the synovial membrane with CD4+ T cells.

Methods: Fifteen patients with seropositive RA, 11 patients with psoriatic arthritis, 20 normal controls, and 9 affected and 13 unaffected siblings from 7 multiplex families with RA were analyzed for clonal proliferation. To investigate this clonal T cell proliferation, CD4+ T cells were purified from peripheral blood and synovial fluid by magnetic bead separation. T cell receptor (TCR) beta-chain sequences were amplified by reverse transcriptase-polymerase chain reaction, using TCR BV and BJ gene segment-specific primer sets. Clonally expanded T cell specificities were identified by size fractionation and sequencing of the amplified product.

Results: All RA patients carried clonally expanded CD4+ T cells in the peripheral blood compartment. Such expanded CD4+ T cell clonotypes were only infrequently observed both in normal individuals (P < 0.0001) and in patients with psoriatic arthritis (P = 0.004). Lymphoproliferation of selected CD4+ T cells was shared by affected and unaffected siblings from RA multiplex families (P = 0.005 and P = 0.0003, respectively, compared with normal controls). Expanded clonotypes persisted for several years and contributed to the T cell infiltrate in the joint. Clonal T cell proliferation involved a diverse spectrum of TCR molecules.

Conclusion: RA patients have an abnormality in the homeostasis of CD4+ T cells, characterized by the emergence of clonally proliferating populations. The presence of clonal outgrowth of selected CD4+ T cells specificities in unaffected siblings of RA patients suggests that oligoclonality of CD4+ T cells is inherited and is a risk factor for, rather than a result of, synovial inflammation.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology*
  • Base Sequence
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Division / genetics
  • Cell Size
  • Clone Cells / chemistry
  • Clone Cells / immunology
  • Clone Cells / pathology
  • Family
  • Humans
  • Immunity, Cellular
  • Lymphocyte Activation
  • Middle Aged
  • Molecular Sequence Data
  • Phenotype
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology


  • Receptors, Antigen, T-Cell