Activated γδ T Cells Promote Dendritic Cell Maturation and Exacerbate the Development of Experimental Autoimmune Uveitis (EAU) in Mice

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.

KEYWORDS:

• Experimental autoimmune uveitis
• γδ T cell
• dendritic cell
• autoreaction
• mouse model

Declaration of interest

The authors report no conflict of interest.

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (81873163, 81674032), the Natural Science Foundation of Shandong Province (ZR2017LH042), the Key Development & Research Program of Shandong Province (2017GSF19110), the Development Project of Science and Technology of Traditional Chinese Medicine of Shandong Province (2015-145, 2015-147), and the Development Project of Medicine and Health Science Technology of Shandong Province (2013WS0251).