title: Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus.
abstract: 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.
authors.affiliation: Immunology and Pharmacotherapy Area, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy. valentina.perri@opbg.net.
authors.forename: Valentina
authors.initials: V
authors.lastname: Perri
authors.affiliation: Immunology and Pharmacotherapy Area, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy. benedetta_russo6@msn.com.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Russo
authors.affiliation: Division of Endocrinology, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. antonino.crino@opbg.net.
authors.forename: Antonino
authors.initials: A
authors.lastname: Crinò
authors.affiliation: Division of Endocrinology, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. riccardo.schiaffini@opbg.net.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Schiaffini
authors.affiliation: Research Laboratories, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy. ezio.giorda@opbg.net.
authors.forename: Ezio
authors.initials: E
authors.lastname: Giorda
authors.affiliation: Division of Endocrinology, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. marco.cappa@opbg.net.
authors.forename: Marco
authors.initials: M
authors.lastname: Cappa
authors.affiliation: Consultant in Immunology, 00100 Rome, Italy. manuela.rosado@immunologyhomepage.com.
authors.forename: Maria Manuela
authors.initials: MM
authors.lastname: Rosado
authors.affiliation: Immunology and Pharmacotherapy Area, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy. alessandra.fierabracci@opbg.net.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D055815:Young Adult
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: T regulatory cells; programmed cell death 1-programmed cell death ligand 1; type 1 diabetes