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Heninger, A.K.* ; Jergens, S. ; Wilhelm, C. ; Beyerlein, A. ; Ziegler, A.-G. ; Bonifacio, E.

A divergent population of autoantigen-responsive CD4+ T cells in infants prior to β cell autoimmunity.

Sci. Transl. Med. 9:eaaf8848 (2017)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Autoimmune diabetes is marked by sensitization to β cell self-antigens in childhood. We longitudinally followed at-risk children from infancy and performed single-cell gene expression in β cell antigen-responsive CD4(+) T cells through pre- and established autoimmune phases. A striking divergence in the gene signature of β cell antigen-responsive naïve CD4(+) T cells from children who developed β cell autoimmunity was found in infancy, well before the appearance of β cell antigen-specific memory T cells or autoantibodies. The signature resembled a pre-T helper 1 (TH1)/TH17/T follicular helper cell response with expression of CCR6, IL21, TBX21, TNF, RORC, EGR2, TGFB1, and ICOS, in the absence of FOXP3, IL17, and other cytokines. The cells transitioned to an IFNG-TH1 memory phenotype with the emergence of autoantibodies. We suggest that the divergent naïve T cell response is a consequence of genetic or environmental priming during unfavorable perinatal exposures and that the signature will guide future efforts to detect and prevent β cell autoimmunity.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Diabetes-associated Autoantibodies; Multiple Islet Autoantibodies; Helper-cells; Increased Risk; Cutting Edge; Type-1; Children; Differentiation; Seroconversion; Activation
ISSN (print) / ISBN 1946-6234
e-ISSN 1946-6242
Journal Science Translational Medicine
Quellenangaben Volume: 9, Issue: 378, Pages: , Article Number: eaaf8848 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Institute of Diabetes and Obesity (IDO)
Institute for Pancreatic Beta Cell Research (IPI)