Universität zu Köln

Liedtke, Katarina, Alter, Christina, Guenther, Anne, Hoevelmeyer, Nadine, Klopfleisch, Robert ORCID: 0000-0002-6308-0568, Naumann, Ronald, Wunderlich, F. Thomas, Buer, Jan, Westendorf, Astrid M. and Hansen, Wiebke (2020). Endogenous CD83 Expression in CD4(+) Conventional T Cells Controls Inflammatory Immune Responses. J. Immunol., 204 (12). S. 3217 - 3227. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606

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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 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 CD8(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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Liedtke, Katarina UNSPECIFIED UNSPECIFIED UNSPECIFIED Alter, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenther, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoevelmeyer, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Klopfleisch, Robert UNSPECIFIED orcid.org/0000-0002-6308-0568 UNSPECIFIED Naumann, Ronald UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Buer, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Westendorf, Astrid M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Wiebke UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-329948
DOI:	10.4049/jimmunol.2000042
Journal or Publication Title:	J. Immunol.
Volume:	204
Number:	12
Page Range:	S. 3217 - 3227
Date:	2020
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	1550-6606
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TOLEROGENIC DENDRITIC CELLS; B-CELL; SOLUBLE FORM; EXPERIMENTAL COLITIS; MURINE CD83; INTERLEUKIN-12; ACTIVATION; LYMPHOCYTES; INDUCTION; MONOCYTES Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32994