Low frequency of GITR+ T cells in ex vivo and in vitro expanded Treg cells from type 1 diabetic patients.
Reported alterations in T(reg) 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(+)CD25(hi) T(reg) cells was similar between samples. However, the yield of sorted T(reg) cells was significantly lower in patients than in controls. When comparing the T(reg)-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 T(reg)-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 T(reg) 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 T(reg)-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' T(reg) cells, suggesting that GITR is a T(reg)-cell marker that would be primarily involved in T(reg)-cell survival rather than in their suppressor function.
Laboratori d'Immunologia Cel·lular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Cristina
C
Xufré
Manuela
M
Costa
Carme
C
Roura-Mir
Eva
E
Codina-Busqueta
Lorena
L
Usero
Eduarda
E
Pizarro
Gabriel
G
Obiols
Dolores
D
Jaraquemada
Mercè
M
Martí
D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D002469:Cell Separation; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
D015704:CD4 Antigens; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit; C491405:TNFRSF18 protein, human
Treg-cell expansion; autoimmunity; cell surface markers