Therapeutic implications of autoimmune vitiligo T cells
Therapeutic implications of autoimmune vitiligo T cells
复制标题
DOI：
10.1016/j.autrev.2006.03.012
复制
发表时间：
2006-08-01
影响因子：
13.6
通讯作者：
Le Poole, I. Caroline
中科院分区：
文献类型：
--
作者：
Oyarbide-Valencia, Kepa;van den Boorn, Jasper G.;Le Poole, I. Caroline
白癜风是一种自身免疫性疾病，表现为皮肤色素沉着的进行性丧失。这种疾病袭击了世界人口的1%，通常发生在青少年时期。色素脱失的白癜风皮肤黑素细胞的进行性损失伴随着含有CD 4+和CD 8 + T淋巴细胞的细胞浸润。具有高亲和力T细胞受体的浸润性细胞毒性T细胞可能逃脱了胸腺中的克隆缺失，从而允许此类T细胞进入循环。通过表达CLA，这些T细胞归巢到皮肤，在那里它们表达I型细胞因子谱并通过颗粒酶/穿孔素途径介导黑素细胞凋亡。可以从皮肤中分离出与剩余黑素细胞并列的T细胞。白癜风T细胞已被证明对以前被认为是T细胞浸润黑色素瘤肿瘤的靶抗原的抗原具有反应性。与现有的黑素瘤衍生的T细胞相比，白癜风T细胞对黑素瘤细胞显示出上级反应性。据认为，编码由白癜风皮肤浸润T细胞表达的TCR的基因可以在黑素瘤T细胞中克隆和表达，从而产生对它们的靶具有高亲和力的循环T细胞库，其可以将免疫应答重新导向肿瘤。(c)2006 Elsevier B. V.保留所有权利。
Vitiligo is an autoimmune disease presenting with progressive loss of skin pigmentation. The disease strikes 1% of the world population, generally during teenage years. The progressive loss of melanocytes from depigmenting vitiligo skin is accompanied by cellular infiltrates containing both CD4+ and CD8+ T lymphocytes. Infiltrating cytotoxic T cells with high affinity T cell receptors have likely escaped clonal deletion in the thymus, allowing such T cells to enter the circulation. Through the expression of CLA, these T cells home to the skin where they express type I-cytokine profiles and mediate melanocyte apoptosis via the granzyme/perforin pathway. T cells found juxtapositionally apposed to remaining melanocytes can be isolated from the skin. Vitiligo T cells have demonstrated reactivity to antigens previously recognized as target antigens for T cells infiltrating melanoma tumors. In a comparison to existing melanoma-derived T cells, vitiligo T cells displayed superior reactivity towards melanoma cells. It is thought that genes encoding the TCRs expressed by vitiligo skin infiltrating T cells can be cloned and expressed in melanoma T cells, thereby generating a pool of circulating T cells with high affinity for their targets that can re-direct the immune response towards the tumor. (c) 2006 Elsevier B.V. All rights reserved.