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. [ABSTRACT FROM AUTHOR]