University of Oulu

Ekman, I., Ihantola, EL., Viisanen, T. et al. Circulating CXCR5−PD-1hi peripheral T helper cells are associated with progression to type 1 diabetes. Diabetologia 62, 1681–1688 (2019).

Circulating CXCR5PD-1hi peripheral T helper cells are associated with progression to type 1 diabetes

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Author: Ekman, Ilse1; Ihantola, Emmi-Leena1; Viisanen, Tyyne1;
Organizations: 1Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, FIN-70210, Kuopio, Finland
2Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Department of Pediatrics, Turku University Hospital, Turku, Finland
4Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
5Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
6Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
7olkhälsan Research Center, Helsinki, Finland
8Department of Pediatrics, Medical Research Center, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland
9Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
10Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
11Clinical Microbiology, Turku University Hospital, Turku, Finland
12Eastern Finland Laboratory Centre (ISLAB), Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
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Language: English
Published: Springer Nature, 2019
Publish Date: 2021-11-24


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 (CXCR5PD-1hi) peripheral T helper (Tph) cells, in human type 1 diabetes.

Methods: The phenotype of blood CXCR5PD-1hi CD4+ T cells was analysed by multicolour flow cytometry. The frequencies of circulating CXCR5PD-1hi 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 CXCR5PD-1hi Tph cells share several features associated with B cell helper function with circulating CXCR5+PD-1hi 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 CXCR5PD-1hi 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.

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Series: Diabetologia
ISSN: 0012-186X
ISSN-E: 1432-0428
ISSN-L: 0012-186X
Volume: 62
Issue: 9
Pages: 1681 - 1688
DOI: 10.1007/s00125-019-4936-8
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The study was supported by the Academy of Finland (Decision no. 307320), the Sigrid Jusélius Foundation, State Research Funding (VTR) and the Finnish Diabetes Research Foundation. The DIPP study was supported by the Academy of Finland (Decision nos 250114 and 286765), the Sigrid Jusélius Foundation and the JDRF.
Copyright information: © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.