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Media type:
E-Article
Title:
Endogenous CD83 Expression in CD4+ Conventional T Cells Controls Inflammatory Immune Responses
Contributor:
Liedtke, Katarina;
Alter, Christina;
Günther, Anne;
Hövelmeyer, Nadine;
Klopfleisch, Robert;
Naumann, Ronald;
Wunderlich, F. Thomas;
Buer, Jan;
Westendorf, Astrid M.;
Hansen, Wiebke
Published:
The American Association of Immunologists, 2020
Published in:
The Journal of Immunology, 204 (2020) 12, Seite 3217-3226
Language:
English
DOI:
10.4049/jimmunol.2000042
ISSN:
0022-1767;
1550-6606
Origination:
Footnote:
Description:
Abstract 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 CD83flox mouse line on BALB/c background, allowing for specific ablation of CD83 in T cells upon breeding with CD4-cre mice. Tregs from CD83flox/flox/CD4-cretg/wt mice had similar suppressive activity as Tregs from CD83flox/flox/CD4-crewt/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+CD45RBhigh T cells from CD83flox/flox/CD4-cretg/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 CD83flox/flox/CD4-crewt/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.