Autoimmune Vitiligo Does Not Require the Ongoing Priming of Naive CD8 T Cells for Disease Progression or Associated Protection against Melanoma
Autoimmune Vitiligo Does Not Require the Ongoing Priming of Naive CD8 T Cells for Disease Progression or Associated Protection against Melanoma
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DOI：
10.4049/jimmunol.1302139
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发表时间：
2014-02-15
影响因子：
4.4
通讯作者：
Turk, Mary Jo
中科院分区：
文献类型：
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作者：
Byrne, Katelyn T.;Zhang, Peisheng;Turk, Mary Jo
白癜风是一种CD 8 T细胞介导的自身免疫性疾病，已被证明可促进记忆T细胞对黑色素瘤的应答的寿命。然而，黑素细胞/黑色素瘤Ag特异性T细胞反应在白癜风背景下持续存在的机制还不清楚。这些研究调查了可能的现象幼稚T细胞启动主机与黑色素瘤启动，自我永存，自身免疫性白癜风。使用幼稚pmel（gp 100（25-33）特异性）转基因CD 8 T细胞，我们证明自身免疫性黑素细胞破坏以Ag依赖性方式诱导皮肤引流淋巴结中的幼稚T细胞增殖。这些pmel T细胞上调CD 44、P-选择素配体和颗粒酶B的表达。然而，它们不下调CD 62 L，也不获得产生IFN-γ的能力，表明缺乏功能性启动。因此，成年胸腺切除小鼠表现出色素脱失的严重程度或动力学没有降低或对黑色素瘤的长期保护，表明幼稚T细胞的持续引发对于白癜风或其相关的抗肿瘤免疫性是不需要的。尽管如此，白癜风过程中CD 4 T细胞的耗竭挽救了能够产生IFN-γ并作为记忆持续存在的幼稚pmel T细胞的引发，表明了调节性T细胞的持续和主导的抑制机制。这项工作揭示了白癜风中自身反应性CD 8 T细胞的复杂调节，并证明了这种自身免疫性疾病的免疫原性总体较差。
Vitiligo is a CD8 T cell-mediated autoimmune disease that has been shown to promote the longevity of memory T cell responses to melanoma. However, mechanisms whereby melanocyte/melanoma Ag-specific T cell responses are perpetuated in the context of vitiligo are not well understood. These studies investigate the possible phenomenon of naive T cell priming in hosts with melanoma-initiated, self-perpetuating, autoimmune vitiligo. Using naive pmel (gp100(25-33)-specific) transgenic CD8 T cells, we demonstrate that autoimmune melanocyte destruction induces naive T cell proliferation in skin-draining lymph nodes, in an Ag-dependent fashion. These pmel T cells upregulate expression of CD44, P-selectin ligand, and granzyme B. However, they do not downregulate CD62L, nor do they acquire the ability to produce IFN-gamma, indicating a lack of functional priming. Accordingly, adult thymectomized mice exhibit no reduction in the severity or kinetics of depigmentation or long-lived protection against melanoma, indicating that the continual priming of naive T cells is not required for vitiligo or its associated antitumor immunity. Despite this, depletion of CD4 T cells during the course of vitiligo rescues the priming of naive pmel T cells that are capable of producing IFN-gamma and persisting as memory, suggesting an ongoing and dominant mechanism of suppression by regulatory T cells. This work reveals the complex regulation of self-reactive CD8 T cells in vitiligo and demonstrates the overall poorly immunogenic nature of this autoimmune disease setting.