Dysregulation of Circular Antigen-Specific T Cells Anergy in Autoimmune Vitiligo
Dysregulation of Circular Antigen-Specific T Cells Anergy in Autoimmune Vitiligo
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自身免疫性白癜风中环状抗原特异性 T 细胞无反应性的失调
DOI：
10.4236/jcdsa.2018.83015
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
I. Katayama
中科院分区：
文献类型：
--
作者：
A. Tanemura;Lingli Yang;I. Katayama
背景：白癜风是一种与黑素细胞丢失相关的自身免疫性疾病；然而，抗原特异性自身免疫与局部氧化应激之间的确切相互作用尚不清楚。最近发现白癜风患者皮损中表达Foxp3的调节性T细胞(Tregs)的迁移能力和数量减少。目的：通过研究进行性白癜风患者外周血中黑素细胞特异性细胞毒性T细胞和功能性Tregs的等价性受损来阐明黑素细胞的T细胞无能状态。材料和方法：10例进展性白癜风患者和10例年龄匹配的健康人。我们分析了进行性白癜风患者的功能性树突状细胞的数量，并将结果与对照组进行了比较。接下来，为了评估Tregs对黑素细胞特异性T淋巴细胞的抑制活性，我们严格纯化了功能Tregs组分和Melan-A特异性CD8+T细胞，并将它们相互共培养。用流式细胞仪计数细胞表面Melan-A特异性CD8+T细胞的数量。此外，还评估了白癜风患者和正常对照组功能树突上具有代表性的耗竭标志物PD-1和CTLA-4的表达。结果：与健康对照组相比，白癜风患者外周血中功能性Tregs的数量没有明显减少。然而，正常人的Tregs培养后细胞毒性T细胞(CTL)增殖显著降低(p<；0.01)，而白癜风患者的Tregs培养后细胞毒性T细胞(CTL)的减少不明显。结论：与健康对照组相比，白癜风患者循环细胞中活化的Tregs对Melan-A特异性CTL的抑制作用减弱。提示伴有Tregs功能障碍的T细胞无能可能参与了白癜风患者对黑素细胞的免疫应答。
Background: Vitiligo is an autoimmune disorder related to melanocyte loss; however, the exact interplay between antigen-specific autoimmunity and local oxidative stress remains unclear. Recently, the migration ability and number of Foxp3-expressing regulatory T cells (Tregs) in lesional skin was found to be reduced in vitiligo patients. Objectives: We aimed to clarify the T cell anergy status of melanocytes by focusing on the impaired equivalence of peripheral melanocyte-specific cytotoxic T cells and functional Tregs in patients with progressive vitiligo. Materials and methods: Ten progressive vitiligo patients and 10 age-matched healthy individuals were enrolled in this study. We analyzed the number of functional Tregs in progressive vitiligo patients and compared the findings with those of controls. Next, to assess the suppressive activity of Tregs on melanocyte-specific T lymphocytes, we strictly purified the functional Tregs fraction and Melan-A-specific CD8+ T cells and co-cultured these cells with each other. The number of Melan-A-specific CD8+ T cells was then counted by FACS. In addition, the expression of the representative exhaustion markers PD-1 and CTLA-4 on functional Tregs was assessed in vitiligo patients and normal controls. Results: The number of functional Tregs itself was not significantly decreased in the blood of vitiligo patients compared to healthy controls. However, the cytotoxic T cell (CTL) proliferation was significantly decreased after cultivation with Tregs from healthy individuals (p < 0.01), and this decrease in CTLs was less marked after cultivation with Tregs from vitiligo patients. Conclusions: We demonstrated a reduced suppressive function of activated Tregs on Melan-A-specific CTLs in the circulating cells of vitiligo patients compared with healthy controls. This result suggests that T cell anergy with Tregs dysfunction may participate in the immune response to melanocytes in vitiligo patients.
影响因子：
32.4
作者：
Miyara, Makoto;Yoshioka, Yumiko;Sakaguchi, Shimon
通讯作者：
Sakaguchi, Shimon