Carbon monoxide-treated dendritic cells decrease [beta]1-integrin induction on CD8 super(+) 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 [beta]-cell peptides protect mice from disease. This protection is peptide-restricted, independent of IL-10 secretion by DCs and of CD4 super(+) T cells. Although no differences were observed in autoreactive CD8 super(+) T-cell function from gCO-treated versus untreated DC-immunized groups, gCO-treated DCs strongly inhibited accumulation of autoreactive CD8 super(+) T cells in the pancreas. Interestingly, induction of [beta]1-integrin was curtailed when CD8 super(+) T cells were primed with gCO-treated DCs, and the capacity of these CD8 super(+) 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.