CD8+ T cells oligoclonally expanded in synovial fluid at onset of spondyloarthropathy selectively proliferate in response to self-antigens: characterization of cell specificities in nonclonal populations.
OBJECTIVE
To characterize putative T cells responsible for the pathogenesis of spondyloarthropathies (SpA).


METHODS
T cells from synovial fluid (SF) and peripheral blood lymphocytes from a patient with chronic ankylosing spondylitis and a patient at the onset of SpA were analyzed for the size of the ss-chain complementarity-determining region 3 to evaluate the degree of clonality. To assess their putative role in triggering disease, immortalized local T cells were tested in lymphocyte proliferation assays against a restricted panel of cell lines.


RESULTS
At disease onset, expansions were detected only in the SF CD8+ T cell subset. As well, SF CD8+ T cells sharing an expanded clonotype (TCR-BV17-J2S1) selectively proliferated when stimulated with autologous-presenting cells. The search for sequence similarities with the expanded clonotype revealed a high homology with the major clonotype in response to influenza A matrix peptide M58-66.


CONCLUSIONS
A CD8+ T cell-mediated antigen-driven mechanism seems to be responsible in the pathogenesis of SpA. Immune response to viral antigens (e.g., from influenza) could be the initiating event in seronegative arthropathies. The combination of spectratyping with RT-PCR and specific Southern blot for the expanded clonotypes on cells derived from mixed lymphocyte cultures was useful to evaluate the proliferative responses of in vivo-expanded cells and to assess T cells involved in the pathogenesis of SpA.
Department of Immunology, Fundación Jiménez Díaz, Madrid, Spain.
Miguel A
MA
Treviño
Emma
E
Teixeiro
Rafael
R
Bragado
D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002999:Clone Cells; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000473:pathology; D013582:Synovial Fluid / Q000166:cytology*; D016176:T-Lymphocyte Subsets
D000956:Antigens, Viral; D001324:Autoantigens; D017260:Receptor-CD3 Complex, Antigen, T-Cell