IFN-gamma enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation.

We compared monocyte-derived dendritic cells and transforming growth factor-beta1-induced Langerhans-like cells (LCs) for their capacity to cross-present exogenous NY-ESO-1 protein/antibody immune complexes to an NY-ESO-1-specific CD8+ T cell clone. In contrast to dendritic cells, LCs were not able to cross-present NY-ESO-1 to the T cell clone constitutively but did so after treatment with IFN-gamma. Remarkably, this IFN-gamma-inducible characteristic was due neither to enhanced antigen uptake nor to facilitated antigen processing in LCs. Rather, IFN-gamma acted at least in part by potentiating the maturation of otherwise refractory LCs, enabling in turn exogenous antigen to reach the processing machinery. This model of conditional cross-presentation establishes an original level of action for IFN-gamma as an effective immune modulator and supports the use of IFN-gamma in protein vaccination strategies targeting LCs.