In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 9, No. 378 ( 2017-02-22)
Abstract:
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 (T H 1)/T H 17/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 -T H 1 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.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.aaf8848
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2017
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