Endogenous CD83 Expression in CD4 Conventional T Cells Controls Inflammatory Immune Responses.

The glycoprotein CD83 is known to be expressed by different immune cells including activated CD4Foxp3 regulatory T cells (Tregs) and CD4Foxp3 conventional T cells. However, the physiological function of endogenous CD83 in CD4 T cell subsets is still unclear. In this study, we have generated a new CD83 mouse line on BALB/c background, allowing for specific ablation of CD83 in T cells upon breeding with CD4-cre mice. Tregs from CD83/CD4-cre mice had similar suppressive activity as Tregs from CD83/CD4-cre wild-type littermates, suggesting that endogenous CD83 expression is dispensable for the inhibitory capacity of Tregs. However, CD83-deficient CD4 conventional T cells showed elevated proliferation and IFN-γ secretion as well as an enhanced capacity to differentiate into Th1 cells and Th17 cells upon stimulation in vitro. T cell-specific ablation of CD83 expression resulted in aggravated contact hypersensitivity reaction accompanied by enhanced CD4 T cell activation. Moreover, adoptive transfer of CD4CD45RB T cells from CD83/CD4-cre mice into Rag2-deficient mice elicited more severe colitis associated with increased serum concentrations of IL-12 and elevated CD40 expression on CD11c dendritic cells (DCs). Strikingly, DCs from BALB/c mice cocultured with CD83-deficient CD4 conventional T cells showed enhanced CD40 expression and IL-12 secretion compared with DCs cocultured with CD4 conventional T cells from CD83/CD4-cre wild-type mice. In summary, these results indicate that endogenous CD83 expression in CD4 conventional T cells plays a crucial role in controlling CD4 T cell responses, at least in part, by regulating the activity of CD11c DCs.