Circulating CXCR5(-)PD-1(hi) peripheral T helper cells are associated with progression to type 1 diabetes

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Ekman , I , Ihantola , E-L , Viisanen , T , Rao , D A , Näntö-Salonen , K , Knip , M , Veijola , R , Toppari , J , Ilonen , J & Kinnunen , T 2019 , ' Circulating CXCR5(-)PD-1(hi) peripheral T helper cells are associated with progression to type 1 diabetes ' , Diabetologia , vol. 62 , no. 9 , pp. 1681-1688 . https://doi.org/10.1007/s00125-019-4936-8

Title: Circulating CXCR5(-)PD-1(hi) peripheral T helper cells are associated with progression to type 1 diabetes
Author: Ekman, Ilse; Ihantola, Emmi-Leena; Viisanen, Tyyne; Rao, Deepak A.; Näntö-Salonen, Kirsti; Knip, Mikael; Veijola, Riitta; Toppari, Jorma; Ilonen, Jorma; Kinnunen, Tuure
Contributor: University of Helsinki, HUS Children and Adolescents
Date: 2019-09
Language: eng
Number of pages: 8
Belongs to series: Diabetologia
ISSN: 0012-186X
URI: http://hdl.handle.net/10138/306335
Abstract: Aims/hypothesis Type 1 diabetes is preceded by a period of asymptomatic autoimmunity characterised by positivity for islet autoantibodies. Therefore, T helper cell responses that induce B cell activation are likely to play a critical role in the disease process. Here, we aimed to evaluate the role of a recently described subset, C-X-C motif chemokine receptor type 5-negative, programmed cell death protein 1-positive (CXCR5(-)PD-1(hi)) peripheral T helper (Tph) cells, in human type 1 diabetes. Methods The phenotype of blood CXCR5(-)PD-1(hi) CD4(+) T cells was analysed by multicolour flow cytometry. The frequencies of circulating CXCR5(-)PD-1(hi) T cells were analysed in a cohort of 44 children with newly diagnosed type 1 diabetes, 40 autoantibody-positive (AAb(+)) at-risk children and 84 autoantibody-negative healthy control children, and the findings were replicated in a separate cohort of 15 children with newly diagnosed type 1 diabetes and 15 healthy control children. Results Circulating CXCR5(-)PD-1(hi) Tph cells share several features associated with B cell helper function with circulating CXCR5(+)PD-1(hi) follicular T helper (Tfh) cells. Moreover, the frequency of circulating Tph cells was increased in children with newly diagnosed type 1 diabetes, especially in those who are positive for multiple autoantibodies. Importantly, circulating Tph cells were also increased in autoantibody-positive at-risk children who later progressed to type 1 diabetes. Conclusions/interpretation Our results demonstrate that circulating CXCR5(-)PD-1(hi) Tph cells are associated with progression to clinical type 1 diabetes. Consequently, Tph cells could have potential both as a biomarker of disease progression and as a target for immunotherapy in type 1 diabetes.
Subject: Autoimmunity
B cells
Follicular T helper cell
Human
Immunophenotyping
Peripheral T helper cell
T cells
Type 1 diabetes
TERTIARY LYMPHOID STRUCTURES
B-CELLS
SUBSET
3121 General medicine, internal medicine and other clinical medicine
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