Low frequency of GITR<sup>+</sup> T cells in ex vivo and in vitro expanded T<inf>reg</inf> cells from type 1 diabetic patients

Cristina Xufré, Manuela Costa, Carme Roura-Mir, Eva Codina-Busqueta, Lorena Usero, Eduarda Pizarro, Gabriel Obiols, Dolores Jaraquemada, Mercè Martí

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21 Citations (Scopus)

Abstract

Reported alterations in Treg cells from type 1 diabetes (T1D) patients led us to a revision of their phenotypical features compared with controls. A fine cytometric analysis was designed for their characterization, using a panel of markers including FOXP3, CTLA4, glucocorticoid-induced TNFR family related (GITR) and CD127. The frequency of peripheral CD4+CD25hi Treg cells was similar between samples. However, the yield of sorted Treg cells was significantly lower in patients than in controls. When comparing the Treg-cell phenotype between samples, the only difference concerned the expression of GITR. A significant decrease of GITR+ cells and GITR mean fluorescence intensity within the Treg-cell population, and to a lesser extent in the effector population, was observed in T1D compared with controls. Moreover, GITR expression was analyzed in several conditions of T-cell activation and differences were only observed in T1D Treg cells versus controls when responding to sub-optimal stimulation, that is, soluble anti-CD3 or medium alone but not in the presence of anti-CD3-/anti-CD28-coated beads. However, expanded T1D Treg-cell-mediated suppression was as efficient as that mediated by their control counterparts, showing no association between their regulatory capacity and the reduced GITR. Our results show a higher susceptibility to apoptosis in patients' versus controls' Treg cells, suggesting that GITR is a Treg-cell marker that would be primarily involved in Treg-cell survival rather than in their suppressor function. © The Japanese Society for Immunology. 2013. All rights reserved.
Original languageEnglish
Pages (from-to)563-574
JournalInternational Immunology
Volume25
Issue number10
DOIs
Publication statusPublished - 1 Oct 2013

Keywords

  • Autoimmunity
  • Cell surface markers
  • T -cell expansion reg

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