High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo.
High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo.
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DOI：
10.1084/jem.188.6.1203
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发表时间：
1998-09-21
期刊：
影响因子：
--
通讯作者：
Cerundolo V
中科院分区：
文献类型：
--
作者：
Ogg GS;Rod Dunbar P;Romero P;Chen JL;Cerundolo V
白癜风是一种自身免疫性疾病，其特征是表皮黑素细胞的损失。使用人类组织相容性白细胞抗原（HLA）I类的四聚体复合物来体外鉴定抗原特异性T细胞，我们在9名HLA-A*0201阳性白癜风患者中的7名中观察到高频率的循环MelanA特异性、A*0201限制性细胞毒性T淋巴细胞（A2-MelanA四聚体+CTL）。分离的A2-MelanA四聚体+CTL能够在体外裂解A*0201匹配的黑素瘤细胞，并且其离体频率与疾病程度相关。相比之下，在所有4名A*0201阴性白癜风患者或6名A* 0201阳性无症状对照中的5名中，均未在体外鉴定到A2-MelanA四聚体+ CTL。最后，我们观察到从白癜风患者分离的A2-MelanA四聚体+CTL表达高水平的皮肤归巢受体，皮肤淋巴细胞相关抗原，这在单个A*0201阳性正常对照中观察到的CTL中不存在。这些数据与皮肤归巢自身反应性黑素细胞特异性CTL在导致自身免疫性白癜风中所见的黑素细胞破坏中的作用一致。自身反应性CTL表面归巢受体的缺乏可能是体内控制外周耐受的机制。
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, A*0201-restricted cytotoxic T lymphocytes (A2–MelanA tetramer+ CTLs) in seven of nine HLA-A*0201–positive individuals with vitiligo. Isolated A2–MelanA tetramer+ CTLs were able to lyse A*0201-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 A*0201-negative vitiligo patients or five of six A*0201-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 A*0201-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.
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DOI：
10.1084/jem.158.1.246
发表时间：
1983-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Naughton GK;Eisinger M;Bystryn JC
通讯作者：
Bystryn JC
DOI：
10.1006/clin.1995.1105
发表时间：
1995-08-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
ERF, GF;TREJOSKALLI, AV;SMYTH, JR
通讯作者：
SMYTH, JR
影响因子：
4.6
作者：
Kemp, EH;Gawkrodger, DJ;Weetman, AP
通讯作者：
Weetman, AP
影响因子：
64.8
作者：
Fuhlbrigge, RC;Kieffer, JD;Kupper, TS
通讯作者：
Kupper, TS
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM