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

• Published in: Diabetologia Vol. 62; no. 9; p. 1681
• 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: Germany 01.09.2019
• Subjects: Biomarkers - metabolism; CD4-Positive T-Lymphocytes - metabolism; Child; Child, Preschool; Coculture Techniques; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Female; Humans; Male; Programmed Cell Death 1 Receptor - metabolism; Receptors, CXCR5 - metabolism; T-Lymphocytes - metabolism; Autoimmunity; Human; Peripheral T helper cell; Type 1 diabetes; Follicular T helper cell; Immunophenotyping; B cells; T cells
• ISSN: 1432-0428

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 ) peripheral T helper (Tph) cells, in human type 1 diabetes. The phenotype of blood CXCR5 PD-1 CD4 T cells was analysed by multicolour flow cytometry. The frequencies of circulating CXCR5 PD-1 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. Circulating CXCR5 PD-1 Tph cells share several features associated with B cell helper function with circulating CXCR5 PD-1 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. Our results demonstrate that circulating CXCR5 PD-1 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.