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

MIGUEL A. TREVIÑO, EMMA TEIXEIRO, and RAFAEL BRAGADO

ABSTRACT.

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.

Conclusion. 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. (J Rheumatol 2004;31:1962-72)

Key Indexing Terms:

SPONDYLOARTHROPATHY
T LYMPHOCYTES
T CELL RECEPTOR
AUTOIMMUNITY

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From the Department of Immunology, Fundación Jiménez Díaz, Madrid, Spain.

Supported by grants from Fondo de Investigaciones Sanitarias and Ministerio de Ciencia y Tecnología (01/0272 and BMC 2002-02644, respectively, to Dr. Bragado); and from Fundación Conchita Rábago (Dr. Treviño) and Comunidad de Madrid (Dr. Teixeiro).

M.A. Treviño, PhD; E. Teixeiro, PhD; R. Bragado, PhD.

Address reprint requests to Dr. R. Bragado, Department of Immunology, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid, Spain. E-mail:rbragado@fjd.es

Submitted November 13, 2003; revision accepted April 14, 2004.

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