Peripheral CD8+ T cell tolerance against melanocytic self-antigens in the skin is regulated in two steps by CD4+ T cells and local inflammation: implications for the pathophysiology of vitiligo.
Peripheral CD8+ T cell tolerance against melanocytic self-antigens in the skin is regulated in two steps by CD4+ T cells and local inflammation: implications for the pathophysiology of vitiligo.
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DOI：
10.1111/j.0022-202x.2004.23538.x
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
J. Steitz;J. Brück;Julia Lenz;Stefanie Büchs;T. Tüting
中科院分区：
文献类型：
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作者：
J. Steitz;J. Brück;Julia Lenz;Stefanie Büchs;T. Tüting
实验证据表明，CD 8+细胞毒性T淋巴细胞（CTL）在白癜风的病理生理学中发挥作用，白癜风是一种皮肤中黑素细胞局灶性丢失的色素沉着疾病。酪氨酸酶相关蛋白2（TRP 2）作为C57 BL/6小鼠中CD 8 + CTL识别的模型黑素细胞自身抗原的发现使我们能够在实验模型中分析CD 8 + T细胞介导的黑素细胞自身免疫破坏的要求。使用两种不同的遗传方法诱导体内细胞免疫，基因枪轰击皮肤和注射重组腺病毒，我们表明，外周耐受性的CD 8 + T细胞识别一个单一的TRP 2衍生的H2-Kb结合肽的调节分两步进行。在诱导阶段，体内TRP 2特异性CD 8 + T细胞的刺激和扩增依赖于CD 4 + T细胞的帮助。在效应阶段，皮肤中黑素细胞的自身免疫破坏取决于局部炎症。我们的研究结果表明，意外刺激CD 8 + CTL识别主要组织相容性复合物I类结合肽来自黑素细胞蛋白的背景下，炎症性皮肤病可能在白癜风的病理生理学中发挥重要作用。
Experimental evidence has suggested a role for CD8+ cytotoxic T lymphocytes (CTL) in the pathophysiology of vitiligo, a pigmentation disorder with focal loss of melanocytes in the skin. The discovery of tyrosinase-related protein 2 (TRP2) as a model melanocytic self-antigen recognized by CD8+ CTL in C57BL/6 mice allowed us to analyze the requirements for CD8+ T cell-mediated autoimmune destruction of melanocytes in an experimental model. Using two different genetic methods for the induction of cellular immunity in vivo, gene gun bombardment of the skin and injection of recombinant adenovirus, we show that peripheral tolerance of CD8+ T cells recognizing a single TRP2-derived H2-Kb-binding peptide is regulated in two steps. In the induction phase, stimulation and expansion of TRP2-specific CD8+ T cells in vivo depend on CD4+ T cell help. In the effector phase, autoimmune destruction of melanocytes in the skin depends on local inflammation. Our results suggest that accidental stimulation of CD8+ CTL recognizing major histocompatibility complex class I-binding peptides derived from melanocytic proteins in the context of an inflammatory skin disease may play an important role in the pathophysiology of vitiligo.