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Human epidermal langerhans cells express the immunoregulatory enzyme indoleamine 2,3-dioxygenase

Authors :
Dagmar von Bubnoff
Huguette Bausinger
Heike Matz
Susanne Koch
Georg Häcker
Osamu Takikawa
Thomas Bieber
Daniel Hanau
Henri de la Salle
Source :
The Journal of investigative dermatology. 123(2)
Publication Year :
2004

Abstract

Langerhans cells (LC) are a special subset of dendritic cells integrating cutaneous immunity. The study of LC function is of major interest not only for efforts of vaccine design and immunotherapy but also for gaining an insight into the pathogenesis of immune-mediated cutaneous diseases and neoplasias. Recently, defined antigen-presenting cells were described that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro and in vivo. Here, we show that stimulation with interferon-gamma (IFN-gamma) induces the expression of functionally active IDO in highly purified human epidermal LC. The induction of IDO after stimulation of LC with IFN-gamma seems to follow a defined kinetic with rapid upregulation followed by a downregulation after about 24 h of culture. Accordingly, proliferation of T cells induced by anti-CD3 antibodies was modulated by supernatants of IFN-gamma-activated human epidermal LC. Importantly, downregulation of T cell proliferation by supernatants of 24 h IFN-gamma-activated LC was prevented by inhibition of IDO. These results indicate that LC not only have the capacity to stimulate but also to inhibit T cells, and suggest that LC possess an immunoregulatory function in promoting T cell tolerance by production of IDO.

Details

ISSN :
0022202X
Volume :
123
Issue :
2
Database :
OpenAIRE
Journal :
The Journal of investigative dermatology
Accession number :
edsair.doi.dedup.....260d3b14d6900eb2fba7a69880fb5493