Ogg G S, Rod Dunbar P, Romero P, Chen J L, Cerundolo V
Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, Oxford, United Kingdom.
J Exp Med. 1998 Sep 21;188(6):1203-8. doi: 10.1084/jem.188.6.1203.
Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. Using tetrameric complexes of human histocompatibility leukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies of circulating MelanA-specific, A0201-restricted cytotoxic T lymphocytes (A2-MelanA tetramer+ CTLs) in seven of nine HLA-A0201-positive individuals with vitiligo. Isolated A2-MelanA tetramer+ CTLs were able to lyse A0201-matched melanoma cells in vitro and their frequency ex vivo correlated with extent of disease. In contrast, no A2-MelanA tetramer+ CTL could be identified ex vivo in all four A0201-negative vitiligo patients or five of six A0201-positive asymptomatic controls. Finally, we observed that the A2-MelanA tetramer+ CTLs isolated from vitiligo patients expressed high levels of the skin homing receptor, cutaneous lymphocyte-associated antigen, which was absent from the CTLs seen in the single A0201-positive normal control. These data are consistent with a role of skin-homing autoreactive melanocyte-specific CTLs in causing the destruction of melanocytes seen in autoimmune vitiligo. Lack of homing receptors on the surface of autoreactive CTLs could be a mechanism to control peripheral tolerance in vivo.
白癜风是一种自身免疫性疾病，其特征为表皮黑素细胞缺失。我们利用人类组织相容性白细胞抗原（HLA）I类四聚体复合物在体外鉴定抗原特异性T细胞，在9例HLA - A0201阳性的白癜风患者中有7例观察到循环中MelanA特异性、A0201限制性细胞毒性T淋巴细胞（A2 - MelanA四聚体阳性CTL）的高频率出现。分离出的A2 - MelanA四聚体阳性CTL在体外能够裂解与A0201匹配的黑色素瘤细胞，其体外频率与疾病程度相关。相比之下，在所有4例A0201阴性的白癜风患者或6例A0201阳性的无症状对照中的5例中，体外均未鉴定出A2 - MelanA四聚体阳性CTL。最后，我们观察到从白癜风患者分离出的A2 - MelanA四聚体阳性CTL表达高水平的皮肤归巢受体——皮肤淋巴细胞相关抗原，而在单一A0201阳性正常对照中所见的CTL中则不存在该抗原。这些数据与皮肤归巢的自身反应性黑素细胞特异性CTL在自身免疫性白癜风中导致黑素细胞破坏的作用一致。自身反应性CTL表面缺乏归巢受体可能是体内控制外周耐受的一种机制。
