Kenefeck, R;
Wang, CJ;
Kapadi, T;
Wardzinski, L;
Attridge, K;
Clough, LE;
Heuts, F;
... Walker, LS; + view all
(2015)
Follicular helper T cell signature in type 1 diabetes.
Journal of Clinical Investigation
, 125
(1)
292- 303.
10.1172/JCI76238.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Follicular helper T cell signature in type 1 diabetes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/JCI76238 |
| Publisher version: | http://dx.doi.org/10.1172/JCI76238 |
| Language: | English |
| Additional information: | Copyright © 2015, American Society for Clinical Investigation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1458481 |
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