Circulating CXCR5-PD-1hi peripheral T helper cells are associated with progression to type 1 diabetes.
Diabetologia
; 62(9): 1681-1688, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-31270583
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Diabetes Mellitus, Type 1
/
Receptors, CXCR5
/
Programmed Cell Death 1 Receptor
Type of study:
Risk_factors_studies
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
Diabetologia
Year:
2019
Document type:
Article
Affiliation country:
Finland
Publication country:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY