Cutting edge:: Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-β-dependent manner

Dendritic celh (DO)play a critical role in both initiating immune responses and in maintaining peripheral tolerance. However, the exact mechanism by which DO instruct/influence the generation of effector vs regulatory T cells is not clear. In this study, we present evidence that TGE-beta, an important immunoregulatory molecule, is present on the surface of ex vivo immature human DO bound by latency-associatedpeptide (LAP). Maturation of DCs upon stimulation with LPS results in loss of membrane-bound LAP and up-regulation of HLA class II and costimulatory molecules. The presence of LAP on immature DO selectively inhibits Th1 cell but not ThI7 cell differentiation and is requiredfor differentiation andlor survival of Toxp3-positive regulatory T cells. Taken togetber, our results indicate that surface expression of TGF-beta on DCs in association with LAP is one of the mechanisms by which immature DO limit T cell activation and thus prevent autoimmune responses.