Joint-derived T cells in rheumatoid arthritis proliferate to antigens present in autologous synovial fluid

Scand J Rheumatol Suppl. 1995;101:169-77. doi: 10.3109/03009749509100922.

Abstract

The histopathological features of rheumatoid joint-inflammation suggest that an antigen-driven activation of T cells plays a central role in the onset and/or perpetuation of the inflammatory process. However, the disease-associated antigens responsible for the activation of T cells in the joint are unknown. In this project we study the response of IL-2 expanded T-cell lines from the synovial fluid (SF) of rheumatoid arthritis (RA) patients against autologous SF in a proliferation assay. Sixteen out of 32 RA patients were found to have CD4+ T cells that proliferate in response to autologous SF. The presence of T cells able to respond to SF antigens in inflamed joints suggests that these T cells play an active role in the pathogenesis of RA. T cell clones reactive to autologous SF were isolated from SF-derived T-cell lines of two RA patients. All clones were of the CD4+, CD8-, alpha/beta+ phenotype. SF-reactivity of T-cell clones from the DR4/DR12-positive RA patient was restricted via the Dw4 subtype of DR4. SF reactivity of T cells of the DR12/DR15 patient was DP-restricted. Some of the T-cell clones responded specifically to autologous and not to allogeneic SF, whereas others revealed responsiveness against a limited number of allogeneic SF samples. The (restricted) specificity of T cells towards autologous SF antigens is indicative for heterogeneity of the epitopes recognized and argues against ubiquitous nonpolymorphic joint constituents as the relevant antigens recognized by the SF-autoreactive T cells.

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Base Sequence
  • Clone Cells
  • Humans
  • Isoantigens / physiology*
  • Joints / pathology*
  • Lymphocyte Activation*
  • Molecular Probes / genetics
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Synovial Fluid / immunology*
  • T-Lymphocytes / physiology*

Substances

  • Isoantigens
  • Molecular Probes
  • Receptors, Antigen, T-Cell, alpha-beta