Carbon monoxide-treated dendritic cells decrease β1-integrin induction on CD8⁺ T cells and protect from type 1 diabetes.
Carbon monoxide (CO) treatment improves pathogenic outcome of autoimmune diseases by promoting tolerance. However, the mechanism behind this protective tolerance is not yet defined. Here, we show in a transgenic mouse model for autoimmune diabetes that ex vivo gaseous CO (gCO)-treated DCs loaded with pancreatic β-cell peptides protect mice from disease. This protection is peptide-restricted, independent of IL-10 secretion by DCs and of CD4(+)  T cells. Although no differences were observed in autoreactive CD8(+)  T-cell function from gCO-treated versus untreated DC-immunized groups, gCO-treated DCs strongly inhibited accumulation of autoreactive CD8(+)  T cells in the pancreas. Interestingly, induction of β1-integrin was curtailed when CD8(+)  T cells were primed with gCO-treated DCs, and the capacity of these CD8(+)  T cells to lyse isolated islet was dramatically impaired. Thus, immunotherapy using CO-treated DCs appears to be an original strategy to control autoimmune disease.
ONIRIS, UMR_A 707 IECM, Nantes, France.
Thomas
T
Simon
Sylvie
S
Pogu
Virginie
V
Tardif
Kevin
K
Rigaud
Séverine
S
Rémy
Eliane
E
Piaggio
Jean-Marie
JM
Bach
Ignacio
I
Anegon
Philippe
P
Blancou
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002248:Carbon Monoxide / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D007108:Immune Tolerance; D050417:Insulin-Secreting Cells / Q000276:immunology*; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology
D001324:Autoantigens; D019012:Integrin beta1; D010446:Peptide Fragments; D002248:Carbon Monoxide