Inflamed joints of patients with rheumatoid arthritis contain T cells that display in vitro proliferation to antigens present in autologous synovial fluid. Functional analysis on the basis of synovial-fluid-reactive T-cell clones and lines.
The immunopathology of inflamed joints in patients with RA is thought to result from an antigen-driven T-cell response. The antigen(s) responsible for the activation of synovial T cells, however, are as yet unidentified. In this study, we tested SF as a potential source of (auto)antigen(s). Five of 15 IL-2-expanded T-cell lines generated from SF cells of RA patients displayed a proliferative response to autologous SF. Five CD4+CD8-alpha beta TCR+SF-reactive T-cell clones obtained from responder T-cell lines were studied in more detail. Three T-cell clones from one RA patient were found to recognize epitopes in autologous SF in the context of DR4(Dw4), and two T-cell clones of another RA patient responded to autologous SF in the context of the HLA-DPB1*0401 gene product. The two DP-restricted clones and one of the DR-restricted clones did not proliferate to 50 SF samples of other RA patients, whereas the remaining DR-restricted clones responded to one allogeneic sample. Sequence analysis demonstrated that the latter clones expressed identical V beta 6.9 + TCR beta chains. This was also found for the (V beta 19+) DP-restricted clones. Proliferation of SF-reactive T cells was not only obtained with SF of the joint that had contained the T cells, but also with autologous SF of other affected joints. Together, these findings indicate that epitopes able to stimulate synovial T cells differ among RA patients, but may be similar within multiple joints of an individual patient. 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.
Res
P C
PC
Department of Rheumatology, University Hospital, Leiden, The Netherlands.
Struijk
L
L
Leow
A
A
Daha
M R
MR
van den Elsen
P C
PC
Breedveld
F C
FC
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013582:Synovial Fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta