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

Proceedings of the National Academy of Sciences of the United States of America
Mitsutoshi MatsuoSacha Gnjatic

Abstract

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.

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