Joint-derived T cells in rheumatoid arthritis proliferate to antigens present in autologous synovial fluid.
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.
Maurice
M M
MM
Dept. of Rheumatology, University Hospital Leiden, The Netherlands.
Res
P C
PC
Leow
A
A
van Hall
T
T
Daha
M R
MR
Struyk
L
L
van den Elsen
P
P
Breedveld
F C
FC
Verweij
C L
CL
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D002999:Clone Cells; D006801:Humans; D007519:Isoantigens / Q000502:physiology*; D007596:Joints / Q000473:pathology*; D008213:Lymphocyte Activation; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013582:Synovial Fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D007519:Isoantigens; D015335:Molecular Probes; D016693:Receptors, Antigen, T-Cell, alpha-beta