Saruhan-Direskeneli G, Uyar F A, Cefle A, Onder S C, Eksioglu-Demiralp E, Kamali S, Inanç M, Ocal L, Gül A
Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Turkey.
Rheumatology (Oxford). 2004 Apr;43(4):423-7. doi: 10.1093/rheumatology/keh063. Epub 2003 Dec 16.
Behçet's disease (BD) is a multisystemic disorder with a possible underlying pathology of immune-mediated vasculitis. Genetic susceptibility associated with HLA-B51 and B2702 has been implicated in its pathogenesis. Considering the recently defined regulatory mechanisms of NK cells through HLA class I binding receptors, we hypothesized that interactions of NK and T cells through the NK receptors may be important in the pathogenesis of BD.
The impact of different expression patterns of HLA-recognizing receptors on NK or T cells was analysed in 51 patients with BD and 32 healthy controls. We used flow cytometry to investigate the expression of KIR3DL1 from the polymorphic killer immunoglobulin-like receptor (KIR) family, which binds a shared HLA-Bw4 motif on HLA-B51 and *2702 alleles, and CD94 from the conserved C-type lectin receptor family, which binds HLA-E. Thirty-three of the BD patients and 19 of the controls carried the same HLA-Bw4 motif.
CD3(+) T cells were increased in patients with BD compared with controls (81 vs 75%, P = 0.001), whereas the NK cells did not show any difference between the two groups. Increased expression of CD94 in BD was observed on CD16(+)CD56(+) cells (66 vs 57, P = 0.04) and on CD3(+) (7.7 vs 4.0, P < 0.001) and CD3(+)CD56(+) (44 vs 35, P = 0.02) T cells. KIR3DL1 expression on the NK and T cells was not statistically different between the two groups. No effect of HLA-Bw4 motif was observed on the expression of CD94 and KIR3DL1 in both the patients and the controls.
The absence of a correlation between KIR3DL1 expression and HLA-Bw4 motif confirms previous work reporting that the expression of these molecules is regulated separately. Increased expression of CD94 may suggest that NK receptors play a pathogenic or regulatory role in BD.
白塞病（BD）是一种多系统疾病，可能存在免疫介导的血管炎潜在病理机制。与HLA - B51和B2702相关的遗传易感性已被认为与其发病机制有关。考虑到最近通过HLA I类结合受体定义的自然杀伤细胞（NK细胞）调节机制，我们推测NK细胞与T细胞通过NK受体的相互作用在BD发病机制中可能很重要。
分析了51例BD患者和32例健康对照中HLA识别受体在NK细胞或T细胞上不同表达模式的影响。我们使用流式细胞术研究多态性杀伤细胞免疫球蛋白样受体（KIR）家族中KIR3DL1的表达，它与HLA - B51和*2702等位基因上共享的HLA - Bw4基序结合，以及保守的C型凝集素受体家族中CD94的表达，它与HLA - E结合。33例BD患者和19例对照携带相同的HLA - Bw4基序。
与对照组相比，BD患者的CD3(+) T细胞增加（81%对75%，P = 0.001），而两组之间的NK细胞没有任何差异。在BD患者中，观察到CD94在CD16(+)CD56(+)细胞上表达增加（66对57，P = 0.04），在CD3(+)（7.7对4.0，P < 0.001）和CD3(+)CD56(+)（44对35，P = 0.02）T细胞上表达增加。两组之间NK细胞和T细胞上KIR3DL1的表达没有统计学差异。在患者和对照中均未观察到HLA - Bw4基序对CD94和KIR3DL1表达有影响。
KIR3DL1表达与HLA - Bw4基序之间缺乏相关性证实了先前的研究报道，即这些分子的表达是分别调节的。CD94表达增加可能表明NK受体在BD中起致病或调节作用。
