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


Authors: Matsuo, M.; Nagata, Y.; Sato, E.; Atanackovic, D.; Valmori, D.; Chen, Y. T.; Ritter, G.; Mellman, I.; Old, L. J.; Gnjatic, S.
Article Title: IFN-γ enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation
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.
Keywords: signal transduction; controlled study; human cell; t lymphocyte; phenotype; cell maturation; dendritic cell; transforming growth factor beta; cell line; membrane proteins; cell differentiation; antigen presentation; dendritic cells; amino acid sequence; molecular sequence data; antigen; antigens, neoplasm; gamma interferon; interferon-gamma, recombinant; immunocytochemistry; transforming growth factor beta1; immunomodulation; enzyme linked immunospot assay; endocytosis; hla-a antigens; major histocompatibility antigen class 1; langerhans cell; langerhans cells; antigen antibody complex; lactacystin; humans; human; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 101
Issue: 40
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2004-10-05
Start Page: 14467
End Page: 14472
Language: English
DOI: 10.1073/pnas.0405947101
PROVIDER: scopus
PMCID: PMC521945
PUBMED: 15383663
DOI/URL:
Notes: Proc. Natl. Acad. Sci. U. S. A. -- Cited By (since 1996):27 -- Export Date: 16 June 2014 -- CODEN: PNASA -- Source: Scopus
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MSK Authors
  1. Mitsutoshi Matsuo
    9 Matsuo
  2. Eiichi Sato
    15 Sato
  3. Yasuhiro Nagata
    11 Nagata
  4. Sacha Gnjatic
    113 Gnjatic
  5. Gerd Ritter
    166 Ritter
  6. Lloyd J Old
    593 Old