ABSTRACT

Our previous study reveals that gamma delta (γδ) T cells were activated and dendritic cells (DCs) underwent maturation during the inflammation phase in experimental autoimmune uveitis (EAU) mice, and the interaction between DCs and γδ T cells may significantly exacerbate the development of EAU. However, the interactions between DCs and γδ T cells that can affect DCs maturation to influence EAU development must be further addressed. In this study we showed that mature DC numbers in TCR-δ^−/− (KO) EAU mice were lower than those in wild-type (WT) C57BL/6 (B6) mice. The γδ T cells harvested from WT EAU mice secreted more interferon-γ (IFN-γ), however, after blocking IFN-γ, the maturation of DCs was significantly downregulated. By contrast, the percentage of IFN-γ- and IL-17-producing CD4⁺ T cells in KO EAU mice decreased to a greater extent than that in WT EAU mice during the inflammatory phase. Additionally, the levels of IFN-γ/IL-17 in serum were in agreement with those of CD4⁺ T cells. Furthermore, after activated γδ T cells injection, the inflammatory symptoms of EAU mice were more aggravated. In vitro co-cultures of both cell types showed that activated γδ T cells may induce DCs to generate higher levels of intracellular cell adhesion molecule-1 (ICAM-1/CD54), CD80, CD83, and CD86. Moreover, co-culture of the two cells may induce the activation of CD4⁺ T cells. Taken together, our results demonstrated that activated γδ T cells may promote DCs maturation and further enhance the generation of Th1/Th17 cells in EAU mice, resulting in exacerbated EAU.

摘要

我们之前的研究表明，在实验性自身免疫性葡萄膜炎 (EAU) 小鼠的炎症阶段，γδ (γδ) T 细胞被激活，树突状细胞 (DC) 成熟，DC 和γδ T 细胞之间的相互作用可能会显着加剧欧盟。然而，必须进一步解决 DCs 和 γδ T 细胞之间可能影响 DCs 成熟以影响 EAU 发育的相互作用。在这项研究中，我们发现 TCR-δ ^-/- (KO) EAU 小鼠的成熟 DC 数量低于野生型 (WT) C57BL/6 (B6) 小鼠。从 WT EAU 小鼠收集的 γδ T 细胞分泌更多的干扰素-γ（IFN-γ），然而，在阻断 IFN-γ 后，DC 的成熟显着下调。相比之下，产生 IFN-γ- 和 IL-17 的 CD4 ⁺的百分比在炎症阶段，KO EAU 小鼠中的 T 细胞比 WT EAU 小鼠中的减少程度更大。此外，血清中 IFN-γ/IL-17 的水平与 CD4 ⁺ T 细胞的水平一致。此外，激活γδ T细胞注射后，EAU小鼠的炎症症状更加加重。两种细胞类型的体外共培养表明，活化的 γδ T 细胞可诱导 DC 产生更高水平的细胞内细胞粘附分子-1 (ICAM-1/CD54)、CD80、CD83 和 CD86。此外，两种细胞的共培养可诱导 CD4 ⁺ T 细胞的活化。综上所述，我们的研究结果表明，活化的 γδ T 细胞可能会促进 DCs 成熟并进一步增强 EAU 小鼠中 Th1/Th17 细胞的产生，导致 EAU 加剧。