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 CD4⁺Foxp3⁺ regulatory T cells (Tregs) and CD4⁺Foxp3^- 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^flox mouse line on BALB/c background, allowing for specific ablation of CD83 in T cells upon breeding with CD4-cre mice. Tregs from CD83^flox/flox/CD4-cre^tg/wt mice had similar suppressive activity as Tregs from CD83^flox/flox/CD4-cre^wt/wt 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 CD4⁺CD45RB^high T cells from CD83^flox/flox/CD4-cre^{tg /wt} 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^flox/flox/CD4-cre^wt/wt 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.