Universität zu Köln

Bacher, P., Kniemeyer, O., Schoenbrunn, A., Sawitzki, B., Assenmacher, M., Rietschel, E., Steinbach, A., Cornely, O. A., Brakhage, A. A., Thiel, A. and Scheffold, A. (2014). Antigen-specific expansion of human regulatory T cells as a major tolerance mechanism against mucosal fungi. Mucosal Immunol., 7 (4). S. 916 - 929. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1935-3456

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Abstract

Foxp3(+) regulatory Tcells (Treg) have a central role for keeping the balance between pro- and anti-inflammatory immune responses against chronically encountered antigens at mucosal sites. However, their antigen specificity especially in humans is largely unknown. Here we used a sensitive enrichment technology for antigen-reactive T cells to directly compare the conventional vs. regulatory CD4(+) T-cell response directed against two ubiquitous mucosal fungi, Aspergillus fumigatus and Candida albicans. In healthy humans, fungus-specific CD4(+) CD25(+) CD127(-) Foxp3(+) Treg are strongly expanded in peripheral blood and possess phenotypic, epigenetic and functional features of thymus-derived Treg. Intriguingly, for A. fumigatus, the strong Treg response contrasts with minimal conventional T-cell memory, indicating selective Treg expansion as an effective mechanism to prevent inappropriate immune activation in healthy individuals. By contrast, in subjects with A. fumigatus allergies, specific Th2 cells were strongly expanded despite the presence of specific Treg. Taken together, we demonstrate a largely expanded Treg population specific for mucosal fungi as part of the physiological human T-cell repertoire and identify a unique capacity of A. fumigatus to selectively generate Treg responses as a potentially important mechanism for the prevention of allergic reactions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bacher, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kniemeyer, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoenbrunn, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sawitzki, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Assenmacher, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinbach, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, O. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brakhage, A. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiel, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheffold, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-435398
DOI:	10.1038/mi.2013.107
Journal or Publication Title:	Mucosal Immunol.
Volume:	7
Number:	4
Page Range:	S. 916 - 929
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1935-3456
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN NAIVE; RESPONSES; IMMUNITY; FOXP3; HOMEOSTASIS; EXPRESSION; INDUCTION; INFECTION; T(H)2; TREG Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43539