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Int. J. Mol. Sci. 2015, 16(9), 22584-22605; doi:10.3390/ijms160922584

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

1
Immunology and Pharmacotherapy Area, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy
2
Division of Endocrinology, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy
3
Research Laboratories, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy
4
Consultant in Immunology, 00100 Rome, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Toshiro Arai
Received: 27 July 2015 / Revised: 3 September 2015 / Accepted: 9 September 2015 / Published: 18 September 2015
(This article belongs to the Special Issue Molecular Research on Obesity and Diabetes)
View Full-Text   |   Download PDF [2667 KB, uploaded 18 September 2015]   |  

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. View Full-Text
Keywords: type 1 diabetes; T regulatory cells; programmed cell death 1-programmed cell death ligand 1 type 1 diabetes; T regulatory cells; programmed cell death 1-programmed cell death ligand 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Perri, V.; Russo, B.; Crinò, A.; Schiaffini, R.; Giorda, E.; Cappa, M.; Rosado, M.M.; Fierabracci, A. Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus. Int. J. Mol. Sci. 2015, 16, 22584-22605.

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