IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04

AUTHORS

Ricardo C. Ferreira, Henry Z. Simons, Whitney S. Thompson, Antony J. Cutler, Xaquin Castro Dopico, Deborah J. Smyth, Meghavi Mashar, Helen Schuilenburg, Neil M. Walker, David B. Dunger, Chris Wallace, John A. Todd, Linda S. Wicker, Marcin L. Pekalski

ABSTRACT

AIMS/HYPOTHESIS: Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes. METHODS: We assessed the production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors. In an additional cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. IL-21 and IL-17 production was also measured in peripheral blood mononuclear cells (PBMCs) from a subset of 46 of the 62 donors immunophenotyped for Tfh. RESULTS: We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). Consistent with this finding, we found a 14.9% increase in circulating Tfh cells in the patients (95% CI 2.9, 26.9; p = 0.016). CONCLUSIONS/INTERPRETATION: These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target. More... »

PAGES

781-790

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00125-015-3509-8

DOI

http://dx.doi.org/10.1007/s00125-015-3509-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039932793

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25652388


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