CHARACTERIZATION OF T-CELLS SPECIFIC FOR AN EPITOPE OF HUMAN 60-KD HEAT-SHOCK-PROTEIN (HSP) IN PATIENTS WITH BEHCETS-DISEASE (BD) IN JAPAN

BD is prevalent in the area of the Silk Route. It has been shown that hsp are involved in the T cell activation in patients with BD in the U K, where this disease has developed sporadically. We have thus examine d whether the T cell response to the hsp-derived peptides may be induc ed in patients with BD in Japan, an east pole of the Silk Route. As wi th patients in the UK, the human 60-kD hsp peptide 336-351 also yielde d vigorous proliferation of T cells in Japanese patients with BD, but neither in normal subjects nor in patients with rheumatoid arthritis ( RA); there was significant association between proliferation by this p eptide and the presence of ocular lesion, but not any other symptoms o f BD. To clarify whether the peptide stimulates T cells as a polyclona l activator, a specific antigen or a superantigen-like substance, we a nalysed T cell receptor (TCR) usage of responding T cells by means of MoAbs specific for TCR V beta subfamily and polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP)-based technique. We found that T cells with certain TCR V beta subfamilies (including V beta 5.2-3, 8, 13.6, 18, 21.3) were increased in circulation and resp onded to the hsp peptide in an antigen-specific fashion. In addition, TCR V beta gene-amplified products of freshly isolated T cells of pati ents with BD formed several bands in the PCR-SSCP analysis; some of th em became prominent after stimulation with the peptide. This suggests that T cells in patients with this disease have already been expanded oligoclonally in vivo, which may be a result of stimulation by trigger ing antigens, including the hsp peptide. In addition, hsp peptide stim ulation induced proinflammatory cytokine mRNA expression in peripheral blood mononuclear cells, including IL-8, tumour necrosis factor-alpha (TNF-alpha) and TNF-beta in eight out of eight patients studied. Take n together, the results suggest that hsp antigen may play a role in th e pathogenesis of BD, not only in the area of the Silk Route, but also outside the Silk Route area.