TY - JOUR
T1 - IFN-γ enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation
AU - Matsuo, Mitsutoshi
AU - Nagata, Yasuhiro
AU - Sato, Eiichi
AU - Atanackovic, Djordje
AU - Valmori, Danila
AU - Chen, Yao Tseng
AU - Ritter, Gerd
AU - Mellman, Ira
AU - Old, Lloyd J.
AU - Gnjatic, Sacha
PY - 2004/10/5
Y1 - 2004/10/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=5144227839&partnerID=8YFLogxK
U2 - 10.1073/pnas.0405947101
DO - 10.1073/pnas.0405947101
M3 - Article
C2 - 15383663
AN - SCOPUS:5144227839
SN - 0027-8424
VL - 101
SP - 14467
EP - 14472
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 40
ER -