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Authors
Kenefeck, RWang, CJ
Kapadi, T
Wardzinski, L
Attridge, K
Clough, LE
Heuts, F
Kogimtzis, A
Patel, S
Rosenthal, M
Ono, M
Sansom, DM
Narendran, P
Walker, LSK
Issue Date
2014-12-08
Metadata
Show full item recordAbstract
The strong genetic association between particular HLA alleles and type 1 diabetes (T1D) indicates a key role for CD4+ T cells in disease; however, the differentiation state of the responsible T cells is unclear. T cell differentiation originally was considered a dichotomy between Th1 and Th2 cells, with Th1 cells deemed culpable for autoimmune islet destruction. Now, multiple additional T cell differentiation fates are recognized with distinct roles. Here, we used a transgenic mouse model of diabetes to probe the gene expression profile of islet-specific T cells by microarray and identified a clear follicular helper T (Tfh) cell differentiation signature. Introduction of T cells with a Tfh cell phenotype from diabetic animals efficiently transferred diabetes to recipient animals. Furthermore, memory T cells from patients with T1D expressed elevated levels of Tfh cell markers, including CXCR5, ICOS, PDCD1, BCL6, and IL21. Defects in the IL-2 pathway are associated with T1D, and IL-2 inhibits Tfh cell differentiation in mice. Consistent with these previous observations, we found that IL-2 inhibited human Tfh cell differentiation and identified a relationship between IL-2 sensitivity in T cells from patients with T1D and acquisition of a Tfh cell phenotype. Together, these findings identify a Tfh cell signature in autoimmune diabetes and suggest that this population could be used as a biomarker and potentially targeted for T1D interventions.Citation
Kenefeck, R., Wang, C. J., Kapadi, T., Wardzinski, L. Attridge, K. et. al. (2014) Follicular helper T cell signature in type 1 diabetes, Journal of Clinical Investigation, 125(1), pp. 292–303.Journal
Journal of Clinical InvestigationDOI
10.1172/JCI76238PubMed ID
25485678Additional Links
https://www.jci.org/articles/view/76238Type
Journal articleLanguage
enISSN
0021-9738EISSN
1558-8238Sponsors
This work was funded by an MRC Senior Fellowship (to L.S.K. Walker), a project grant from JDRF (to L.S.K. Walker and P. Narendran), and a studentship from Diabetes UK (to L.S.K. Walker and P. Narendran). L. Wardzinski and A. Kogimtzis were supported by a Wellcome Trust project grant (to L.S.K. Walker). M. Ono is a BBSRC David Philips fellow.ae974a485f413a2113503eed53cd6c53
10.1172/JCI76238
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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/
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