Identification and functional characterization of CD8+ T regulatory cells in type 1 diabetes patients.
Adolescent
Adult
Biomarkers
/ blood
CD8-Positive T-Lymphocytes
/ classification
Case-Control Studies
Cell Proliferation
/ drug effects
Child
Child, Preschool
Diabetes Mellitus, Type 1
/ blood
Female
Glycated Hemoglobin
/ metabolism
Humans
Immunotherapy
In Vitro Techniques
Ionomycin
/ pharmacology
Male
Pilot Projects
Programmed Cell Death 1 Receptor
/ metabolism
T-Lymphocytes, Regulatory
/ classification
Tetradecanoylphorbol Acetate
/ pharmacology
Young Adult
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
29
10
2018
accepted:
02
01
2019
entrez:
17
1
2019
pubmed:
17
1
2019
medline:
23
10
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30650147
doi: 10.1371/journal.pone.0210839
pii: PONE-D-18-31176
pmc: PMC6334945
doi:
Substances chimiques
Biomarkers
0
Glycated Hemoglobin A
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
hemoglobin A1c protein, human
0
Ionomycin
56092-81-0
Tetradecanoylphorbol Acetate
NI40JAQ945
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0210839Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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