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

Our previous study reveals that gamma delta (gamma delta) 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 gamma delta T cells may significantly exacerbate the development of EAU. However, the interactions between DCs and gamma delta 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-delta(-/-) (KO) EAU mice were lower than those in wild-type (WT) C57BL/6 (B6) mice. The gamma delta T cells harvested from WT EAU mice secreted more interferon-gamma (IFN-gamma), however, after blocking IFN-gamma, the maturation of DCs was significantly downregulated. By contrast, the percentage of IFN-gamma- 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-gamma/IL-17 in serum were in agreement with those of CD4(+) T cells. Furthermore, after activated gamma delta T cells injection, the inflammatory symptoms of EAU mice were more aggravated. In vitro co-cultures of both cell types showed that activated gamma delta 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 gamma delta T cells may promote DCs maturation and further enhance the generation of Th1/Th17 cells in EAU mice, resulting in exacerbated EAU.