Sakane T
Department of Immunology, St. Marianna University, School of Medicine, Kanagawa, Japan.
Int Rev Immunol. 1997;14(1):89-96. doi: 10.3109/08830189709116847.
There are many distinct differences between Behçet's disease of Silk Route and that of outside Silk Route; genetic factors, role of neutrophils, and severity of this disease. We have thus emphasized that we prefer the term "Behçet's syndrome" rather than "Behçet's disease". In this chapter, Behçet's disease seen along the Silk Route will be mainly discussed. HLA-B51 molecules themselves may be responsible, at least in part, for the neutrophil hyperfunction in Behçet's disease; a significant correlation was observed between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, in both humans and HLA-B transgenic mice. T cells in this disease, proliferated vigorously in response to a specific peptide of human heat shock protein (HSP)-60; however, T cells from normal subjects or patients with rheumatoid arthritis, did not. This peptide has the amino acid sequence of 336-351 of human HSP-60, which is similar, but not identical to specific peptide of mycobacterial HSP-65. We have further analyzed T cell receptor (TCR) usage of HSP-responsive T cells by means of TCR V beta subfamily specific monoclonal antibodies and polymerase chain reaction and single strand conformation polymorphism-based technique. We found that T cells with specific TCR V beta subfamilies proliferated and increased in number in response to the peptide by an antigen-specific fashion. The result of recurrent exposure to the HSP may break the tolerance to self-HSP, and provoke T cell responses to self- and microbial-HSP. Such T cells produced Th1-like proinflammatory and/or inflammatory cytokines. This leads to tissue injury, possibly via delayed-type hypersensitivity reaction, macrophage activation, and activation and/or recruitment of neutrophils. Our data shed a new light on the autoimmune nature of Behçet's disease; a novel multistep molecular mimicry mechanisms may induce and/or exacerbate Behçet's disease by bacterial antigens that activate T cells previously educated by self-peptides of HSP. This would lead to positive selection of autoreactive T cells in this disease.
丝绸之路沿线的白塞病与丝绸之路以外地区的白塞病存在许多明显差异；包括遗传因素、中性粒细胞的作用以及该病的严重程度。因此，我们强调更倾向于使用“白塞综合征”这一术语而非“白塞病”。在本章中，将主要讨论丝绸之路沿线所见的白塞病。HLA - B51分子本身可能至少部分导致了白塞病中的中性粒细胞功能亢进；在人类和HLA - B转基因小鼠中，无论疾病是否存在，均观察到中性粒细胞功能亢进与HLA - B51表型的拥有之间存在显著相关性。该疾病中的T细胞对人热休克蛋白（HSP）- 60的特定肽段有强烈增殖反应；然而，正常受试者或类风湿性关节炎患者的T细胞则无此反应。该肽段具有人HSP - 60的336 - 351氨基酸序列，与分枝杆菌HSP - 65的特定肽段相似但不完全相同。我们通过TCR Vβ亚家族特异性单克隆抗体以及基于聚合酶链反应和单链构象多态性的技术，进一步分析了HSP反应性T细胞的T细胞受体（TCR）使用情况。我们发现具有特定TCR Vβ亚家族的T细胞以抗原特异性方式对该肽段产生增殖并数量增加。反复接触HSP的结果可能会打破对自身HSP的耐受性，并引发T细胞对自身和微生物HSP的反应。此类T细胞产生Th1样促炎和/或炎症细胞因子。这可能通过迟发型超敏反应、巨噬细胞激活以及中性粒细胞的激活和/或募集导致组织损伤。我们的数据为白塞病的自身免疫性质提供了新的线索；一种新的多步骤分子模拟机制可能通过细菌抗原诱导和/或加剧白塞病，这些细菌抗原激活先前由HSP自身肽段致敏的T细胞。这将导致该疾病中自身反应性T细胞的阳性选择。
