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Normal human T cells proliferate vigorously when stimulated with autologous non-T cells. This autologous mixed lymphocyte reaction (MLR) between T and non-T cells was defective in patients with active systemic lupus erythematosus (SLE) In contrast, T cells and non-T cells from active SLE patients behaved normally as responding and stimulating cells, respectively, in the allogeneic MLR. Systemic lupus erythematosus (SLE) is a complex multisystem autoimmune disease. One of its most prominent features is the presence of a wide variety of autoantibodies in the serum. In addition, several T cell defects have been described in patients with active SLE. It has been postulated that the excessive production of autoantibodies is due to some abnormality in B cell regulation by T cells (1, 2). More specifically, evidence has been presented to suggest a relative lack of suppressor T cell function in such patients (3-5).In the course of our studies of suppressor T cell function in patients with SLE (5), we made the unexpected observation that, when lymphocytes from patients with SLE were used, the autologous mixed lymphocyte reaction (MLR) failed to occur.That is, whereas T cells from normal individuals proliferate vigorously in response to autologous non-T cells, T cells from SLE patients failed to proliferate normally in response to autologous non-T cells. In these studies we have investigated the reason for this defect in patients with SLE.Because it has been recently proposed that "autologous MLR reflect a mechanism by which T lymphocytes regulate lymphocyte function" (6), the absence of such a reaction in the lymphocytes of patients with SLE is particularly provoca-

Objective. To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behqet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behqet's disease patients, from HLA-B51 positive healthy individuals, and from HLA-B51 transgenic mice, Methods. Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2',7'-dichlorofluorescin diacetate into dichlorofluorescein, induced by superoxide in the neutrophils.Results. A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-BS1 transgenic mice, but not those from HLA-B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide.Conclusion. The HLA-BS1 molecule itself may be responsible, at least in part, for neutrophil hyperfunction in Behqet's disease.

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SUMMARYBD 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 UK, where this disease has developed sporadically. We have thus examined whether the T cell response to the hsp-derived peptides may be induced in patients with BD in Japan, an east pole of the Silk Route. As with patients in the UK, the human 60-kD hsp peptide 336-351 also yielded 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 peptide and the presence of ocular lesion, but not any other symptoms of BD. To clarify whether the peptide stimulates T cells as a polyclonal activator, a specific antigen or a superantigen-like substance, we analysed T cell receptor (TCR) usage of responding T cells by means of MoAbs specific for TCR Vb subfamily and polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP)-based technique. We found that T cells with certain TCR Vb subfamilies (including Vb5.2-3, 8, 13.6, 18, 21.3) were increased in circulation and responded to the hsp peptide in an antigen-specific fashion. In addition, TCR Vb gene-amplified products of freshly isolated T cells of patients with BD formed several bands in the PCR-SSCP analysis; some of them 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 triggering antigens, including the hsp peptide. In addition, hsp peptide stimulation induced proinflammatory cytokine mRNA expression in peripheral blood mononuclear cells, including IL-8, tumour necrosis factor-alpha (TNF-a) and TNF-b in eight out of eight patients studied. Taken together, the results suggest that hsp antigen may play a role in the pathogenesis of BD, not only in the area of the Silk Route, but also outside the Silk Route area.