Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus

• Published in: International journal of molecular sciences Vol. 16; no. 9; pp. 22584 - 22605
• Main Authors: Perri, Valentina, Russo, Benedetta, Crinò, Antonino, Schiaffini, Riccardo, Giorda, Ezio, Cappa, Marco, Rosado, Maria Manuela, Fierabracci, Alessandra
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18-09-2015; MDPI
• Subjects: Adolescent; Adult; Apoptosis; Cellular biology; Child; Child, Preschool; Diabetes; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Female; Humans; Ligands; Lymphocyte Activation; Male; Pancreas; Programmed Cell Death 1 Receptor - analysis; Programmed Cell Death 1 Receptor - immunology; programmed cell death 1-programmed cell death ligand 1; T regulatory cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; type 1 diabetes; Young Adult; T regulatory cells; type 1 diabetes; programmed cell death 1-programmed cell death ligand 1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms160922584

Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4⁺CD25⁺ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of CD4⁺CD25high T cells in autoimmunity and their molecular mechanisms remain the subject of investigation. We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. Percentages of total PD-1⁺, PD-1low and PD-1high expressing T regulatory cells did not change in patients and in controls. After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1⁺, PD-1low and PD-1high expressing cells were lower in patients. Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface.