Identification and functional characterization of CD8(+) T regulatory cells in type 1 diabetes patients

Type 1 diabetes is an autoimmune disease where autoreactive T lymphocytes destroy pancreatic beta cells. We previously reported a defect in CD4(+) Tregs cell proliferation and reduced CD4(+) Tregs PD-1 expression in patients. Another ‘memory-like’ regulatory subset, CD8(+) Tregs, evaluated as CD8(+)CD25(+)FOXP3(+), has recently raised interest for their effective suppressive activity. Different CD8(+) T cell populations, their proliferation capacity and expression of PD-1 molecule were evaluated by flow-cytometer analysis in newly diagnosed, long-term Type 1 diabetes patients compared to healthy normal donors. Under basal conditions, CD8(+) Tregs and CD8(+) Teffs were seemingly represented among study groups while there was evidence of diminished expression of PD-1 in Teff subsets of long-term patients. After 3 days of PMA/ionomycin stimulation, patients CD8(+) Tregs showed decreased percentage in respect to control group. CD8(+) Teffs were instead increased in long-term diabetics versus controls. PD-1(+)CD8(+) Tregs were represented at a much lower percentage in long-term diabetic patients, in respect to controls. Importantly, patients CD8(+) Tregs and CD8(+) Teffs presented a significant proliferation defect in respect to the control group. In conclusion, our study indicates that a defect of CD8(+) Tregs is observed in diabetics. This subset could thus represent a novel target of immunotherapy in patients.