DC expressing transgene Foxp3 are regulatory APC

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 na?̈ve, 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 na?̈ve 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. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.