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Diabetologia. 2019 Jul 3. doi: 10.1007/s00125-019-4936-8. [Epub ahead of print]

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

Author information

1
Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, FIN-70210, Kuopio, Finland.
2
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
3
Department of Pediatrics, Turku University Hospital, Turku, Finland.
4
Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
5
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
6
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
7
Folkhälsan Research Center, Helsinki, Finland.
8
Department of Pediatrics, Medical Research Center, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland.
9
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.
10
Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
11
Clinical Microbiology, Turku University Hospital, Turku, Finland.
12
Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, FIN-70210, Kuopio, Finland. tuure.kinnunen@uef.fi.
13
Eastern Finland Laboratory Centre (ISLAB), Kuopio, Finland. tuure.kinnunen@uef.fi.

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

METHODS:

The phenotype of blood CXCR5-PD-1hi CD4+ T cells was analysed by multicolour flow cytometry. The frequencies of circulating CXCR5-PD-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 CXCR5-PD-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 CXCR5-PD-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.

KEYWORDS:

Autoimmunity; B cells; Follicular T helper cell; Human; Immunophenotyping; Peripheral T helper cell; T cells; Type 1 diabetes

PMID:
31270583
DOI:
10.1007/s00125-019-4936-8

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