| First Author | Liedtke K | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 12 | Pages | 3217-3226 |
| PubMed ID | 32341061 | Mgi Jnum | J:291367 |
| Mgi Id | MGI:6444952 | Doi | 10.4049/jimmunol.2000042 |
| Citation | Liedtke K, et al. (2020) Endogenous CD83 Expression in CD4(+) Conventional T Cells Controls Inflammatory Immune Responses. J Immunol 204(12):3217-3226 |
| abstractText | 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-gamma 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. |
