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†, and
- Sacha Gnjatic†,††
- †Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; §Ludwig Institute Clinical Trial Center, Columbia University College of Physicians and Surgeons, New York, NY 10032; ¶Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021; ∥Ludwig Institute for Cancer Research, Departments of Cell Biology and Immunobiology, Yale University School of Medicine, New Haven, CT 06520
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Contributed by Lloyd J. Old, August 13, 2004
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.
Footnotes
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↵ †† To whom correspondence should be addressed at: Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 32, New York, NY 10021. E-mail: gnjatics{at}mskcc.org.
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↵ ‡ Present address: Department of Transplantation and Digestive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
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Abbreviations: DC, dendritic cell; mo-DC, monocyte-derived DC; IC, immune complex; LC, Langerhans-like cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; elispot, enzyme-linked immunospot; FACS, fluorescence-activated cell sorter; LPS, lipopolysaccharide.
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Freely available online through the PNAS open access option.
- Copyright © 2004, The National Academy of Sciences
