DC expressing transgene Foxp3 are regulatory APC

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Abstract
Tolerogenic DC and suppressive Foxp3+ Treg play important roles in preventing autoimmunity and allograft rejection. We report that (adenovirus mediated) ectopic expression of Foxp3 in human DC (i.e. DC.Foxp3) yields an APC that severely limits T‐cell proliferation and type‐1 immune responses from the naïve, but not memory, pool of responder T cells in vitro. In marked contrast, the frequencies of type‐2 and Treg responses were dramatically increased after stimulation of naïve T cells with DC.Foxp3 versus control DC. DC.Foxp3‐induced CD4+CD25+ Treg cells potently suppressed the proliferation of, and IFN‐γ production from, CD4+ and CD8+ responder T cells. Notably, the immunosuppressive biology of DC.Foxp3 was effectively normalized by addition of 1‐methyl‐tryptophan or neutralizing anti‐TGF‐β1 Ab during the period of T‐cell priming. These data suggest the potential utility of regulatory DC.Foxp3 and/or DC.Foxp3‐induced CD4+CD25+ Treg as translational agents for the amelioration or prevention of pathology in the setting of allograft transplantation and/or autoimmunity.