Tsuchiyama Junjiro, Yoshino Tadashi, Toba Ken, Harada Naoki, Nishiuchi Ritsuo, Akagi Tadaatsu, Furukawa Tatsuo, Takahashi Masuiro, Fuse Ichiro, Aizawa Yoshifusa, Harada Mine
First Department of Internal Medicine, Niigata University School of Medicine, 1-754 Asahi-machi, Niigata 951, Japan.
Br J Haematol. 2002 Aug;118(2):654-62. doi: 10.1046/j.1365-2141.2002.03608.x.
Cutaneous lymphocyte antigen (CLA) has been reported to be expressed mainly by memory/effector T lymphocytes infiltrating inflammatory skin lesions and cutaneous T-cell lymphoma. It has been suggested that CLA is a specific homing receptor, facilitating the T-cell migration into skin lesions, and also an indicator of the skin-homing T-cell subset. In the present study, we investigated the expression of CLA in natural killer (NK) cells defined phenotypically as surface CD3- and CD56+ cells in peripheral blood. CLA was definitely expressed on CD3-CD56+ cells at a level comparable to CD3+ cells in peripheral blood of normal Japanese volunteers. After in vitro stimulation of peripheral blood mononuclear cells with interleukin 2 (IL-2) and IL-12, there was a significant increase in the number and percentage of CLA+ NK cells but not CLA+ T cells (P < 0.01). To analyse the characteristics of CLA expressed by NK cells, we investigated a CLA+ NK-leukaemia cell line, NK-YS, established from a patient with NK leukaemia/lymphoma with skin infiltration. In the in vitro study, the CLA-expressing NK-leukaemic cell line bound to E-selectin-transfected cells and was inhibited by HECA 452 antibody or neuraminidase treatment of leukaemic cells. These findings suggest that CLA expressed by NK cells is a homing receptor for the E-selectin molecule and may explain skin infiltration by NK cells and NK lymphoma cells analogous to T cells. An NK-cell subset expressing CLA must play an important role in host defence against microorganisms and neoplasms in skin lesions.
据报道,皮肤淋巴细胞抗原(CLA)主要由浸润炎性皮肤病变和皮肤T细胞淋巴瘤的记忆/效应T淋巴细胞表达。有人提出,CLA是一种特异性归巢受体,有助于T细胞迁移到皮肤病变中,也是皮肤归巢T细胞亚群的一个指标。在本研究中,我们调查了CLA在表型上定义为外周血中表面CD3阴性和CD56阳性细胞的自然杀伤(NK)细胞中的表达情况。在正常日本志愿者的外周血中,CLA在CD3阴性CD56阳性细胞上确实有表达,其水平与CD3阳性细胞相当。用白细胞介素2(IL-2)和IL-12体外刺激外周血单个核细胞后,CLA阳性NK细胞的数量和百分比显著增加,但CLA阳性T细胞没有增加(P<0.01)。为了分析NK细胞表达的CLA的特征,我们研究了一株CLA阳性的NK白血病细胞系NK-YS,它是从一名有皮肤浸润的NK白血病/淋巴瘤患者中建立的。在体外研究中,表达CLA的NK白血病细胞系与转染E-选择素的细胞结合,并被HECA 452抗体或对白血病细胞进行神经氨酸酶处理所抑制。这些发现表明,NK细胞表达的CLA是E-选择素分子的归巢受体,可能解释了NK细胞和NK淋巴瘤细胞与T细胞类似的皮肤浸润现象。表达CLA的NK细胞亚群在宿主抵御皮肤病变中的微生物和肿瘤方面必定发挥着重要作用。