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

PLoS One. 2019 Jan 16;14(1):e0210839. doi: 10.1371/journal.pone.0210839. eCollection 2019.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • CD8-Positive T-Lymphocytes / classification
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Cell Proliferation / drug effects
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Immunotherapy
  • In Vitro Techniques
  • Ionomycin / pharmacology
  • Male
  • Pilot Projects
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes, Regulatory / classification
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Young Adult


  • Biomarkers
  • Glycated Hemoglobin A
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • hemoglobin A1c protein, human
  • Ionomycin
  • Tetradecanoylphorbol Acetate

Grant support

This work was supported by Italian Ministry of Health Ricerca corrente RC201702P003967 (AF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.