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

Mitsutoshi Matsuo, Yasuhiro Nagata, Eiichi Sato, Djordje Atanackovic, Danila Valmori, Yao Tseng Chen, Gerd Ritter, Ira Mellman, Lloyd J. Old, Sacha Gnjatic

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

We compared monocyte-derived dendritic cells and transforming growth factor-β1-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-γ. Remarkably, this IFN-γ-inducible characteristic was due neither to enhanced antigen uptake nor to facilitated antigen processing in LCs. Rather, IFN-γ 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-γ as an effective immune modulator and supports the use of IFN-γ in protein vaccination strategies targeting LCs.

Original languageEnglish
Pages (from-to)14467-14472
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number40
DOIs
StatePublished - 5 Oct 2004
Externally publishedYes

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