State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Eur J Immunol. 2023 Dec;53(12):e2350574. doi: 10.1002/eji.202350574. Epub 2023 Sep 17.
Various regulatory CD8 T-cell subsets have been proposed for immune tolerance and have been implicated in controlling autoimmune diseases. However, their phenotypic identities and suppression mechanisms are not yet understood. This study found that coculture of T-cell receptor (TCR)- or interferon (IFN)-β-activated CD8 T cells significantly suppressed the cytokine production of Th1 and Th17 cells. By experimenting with the experimental autoimmune uveitis (EAU), we found that adoptive transfer of TCR or IFN-β-activated CD8 T cells significantly lessened disease development in an IFN-γ-dependent manner with a decreased uveitogenic Th1 and Th17 response. Interestingly, after adoptive transfer into the EAU mice, the IFN-γ CD8 T cells were recruited more efficiently into the secondary lymphoid organs during the disease-priming phase. This recruitment depends on the IFN-γ-inducible chemokine receptor CXCR3; knocking out CXCR3 abolishes the protective effect of CD8 T cells in EAU. In conclusion, we identified the critical role of IFN-γ for CD8 T cells to inhibit Th1 and Th17 responses and ameliorate EAU. CXCR3 is necessary to recruit IFN-γ CD8 T cells to the secondary lymphoid organ for the regulation of autoreactive Th1 and Th17 cells.
各种调节性 CD8 T 细胞亚群已被提出用于免疫耐受，并被认为与控制自身免疫性疾病有关。然而，它们的表型特征和抑制机制尚不清楚。本研究发现，T 细胞受体（TCR）或干扰素（IFN）-β 激活的 CD8 T 细胞的共培养显著抑制了 Th1 和 Th17 细胞的细胞因子产生。通过实验性自身免疫性葡萄膜炎（EAU），我们发现，TCR 或 IFN-β 激活的 CD8 T 细胞的过继转移以 IFN-γ 依赖性方式显著减轻疾病发展，伴有葡萄膜炎症性 Th1 和 Th17 反应降低。有趣的是，在 EAU 小鼠中过继转移后，IFN-γ CD8 T 细胞在疾病引发阶段更有效地募集到次级淋巴器官中。这种募集依赖于 IFN-γ 诱导的趋化因子受体 CXCR3；敲除 CXCR3 会消除 CD8 T 细胞在 EAU 中的保护作用。总之，我们确定了 IFN-γ 对 CD8 T 细胞抑制 Th1 和 Th17 反应和改善 EAU 的关键作用。CXCR3 对于招募 IFN-γ CD8 T 细胞到次级淋巴器官以调节自身反应性 Th1 和 Th17 细胞是必要的。
