Identification of CD8+CD25+FOXP3+ regulatory T cells in Type 1 Diabetes: assembling the puzzle in the disease etiopathogenesis

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Abstract Summary

 

Insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) is an autoimmune disease where autoreactive T lymphocytes destroy pancreatic beta cells. Common human autoimmune diseases show quantitative or qualitative T regulatory (Treg) defects. We previously reported a defect in CD4+ Tregs cell proliferation and reduced CD4+ Tregs PD-1 expression in diabetic patients (Perri 2015). Further, another regulatory subset, CD8+ Tregs, endowed with immunosuppressive functions, has recently raised interest. These cells, evaluated as CD8+CD25+FOXP3+ cells, are represented as a much lower percentage (below 1%) of population in human PBMC in respect to CD4+ Tregs (8%). Despite their reduced abundancy, CD8+ Tregs require serious consideration in the regulation of immune responses due to their effective suppressive activity.

 

Different CD8+ T cell populations, their proliferation capacity and expression in PD-1 molecule were evaluated by flow-cytometer analysis in a cohort of 31 T1D patients, 18 newly-diagnosed and 13 long-term, compared to 20 healthy donors. The various subsets were studied under basal conditions and after 3 and 5 days of PMA/ionomycin stimulation.

 

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 the patients eff cells. After 3 days of PMA/ionomycin stimuli patients CD8+ Tregs showed decreased percentage in respect to control group. PD-1+CD8+ Tregs were represented as a much lower percentage in diabetic patients, in respect to control subjects. Importantly, patients CD8+ Tregs and CD8+ Teffs presented a significant proliferation defect in respect to the control group. In conclusion, CD8+ Tregs could represent a novel target of immunotherapy in T1D patients.

 

Submission ID :
IDS70173
Submission Type
Abstract Topics
Children's Hospital Bambino Gesù, Rome, Italy
Type 1 Diabetes Center, Infectivology and Clinical Trials Research Division, Children's Hospital Bambino Gesù, Rome, Italy
Type 1 Diabetes Center, Infectivology and Clinical Trials Research Division, Children's Hospital Bambino Gesù, Rome, Italy
Division of Endocrinology, Children's Hospital Bambino Gesù, Rome, Italy
Division of Endocrinology, Children's Hospital Bambino Gesù, Rome, Italy
Immunology Consultant, Rome, Italy
Research laboratories, Children's Hospital Bambino Gesù, Rome, Italy

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Event dates:
Thursday 25 October - Monday 29 October 2018

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Monday 14 May 2018

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July 2018

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Monday 3 September 2018

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Monday 15 October 2018

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