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

• Published in: Diabetologia Vol. 62; no. 9; pp. 1681 - 1688
• Main Authors: Ekman, Ilse, Ihantola, Emmi-Leena, Viisanen, Tyyne, Rao, Deepak A., Näntö-Salonen, Kirsti, Knip, Mikael, Veijola, Riitta, Toppari, Jorma, Ilonen, Jorma, Kinnunen, Tuure
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2019; Springer Nature B.V
• Subjects: Apoptosis; Autoantibodies; Autoimmunity; Beta cells; CD4 antigen; Cell activation; Cell death; Chemokines; Children; CXCR5 protein; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Flow cytometry; Helper cells; Human Physiology; Immunotherapy; Internal Medicine; Lymphocytes T; Medicine; Medicine & Public Health; Metabolic Diseases; Phenotypes; Autoimmunity; Human; Peripheral T helper cell; Type 1 diabetes; Follicular T helper cell; Immunophenotyping; B cells; T cells
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-019-4936-8

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.