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Original Article

^a Department of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
^b Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
^c Department of Immunology, Novartis Research Institute, A-1235 Vienna, Austria
Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany.49-9131-85-2210149-9131-85-26182

jmhauber{at}viro.med.uni-erlangen.de

Dendritic cells (DCs), nature's adjuvant, must mature to sensitize T cells. However, although the maturation process is essential, it is not yet fully understood at the molecular level. In this study, we investigated the course of expression of the unique hypusine-containing protein eukaryotic initiation factor 5A (eIF-5A), which is part of a particular RNA nuclear export pathway, during in vitro generation of human DCs. We show that eIF-5A expression is significantly upregulated during DC maturation. Furthermore, an inhibitor of the hypusine modification, GC7 (N¹-guanyl-1,7-diaminoheptane), prevents CD83 surface expression by apparently interfering with nucleocytoplasmic translocation of the CD83 mRNA and, importantly, significantly inhibits DC-mediated T lymphocyte activation. The data presented suggest that CD83 mRNA is transported from the nucleus to the cytoplasm via a specific nuclear export pathway and that hypusine formation appears to be essential for the maturation of functional DCs. Therefore, pharmacological interference with hypusine formation may provide a new possibility to modulate DC function.

Key Words: dendritic cells • CD83 • hypusine • eIF-5A • nuclear export

D. Bevec's current address is Axxima Pharmaceuticals AG, Am Klopferspitz 19, D-82152 Martinsried, Germany.

Abbreviations used in this paper: AREs, AU-rich elements; DCs, dendritic cells; eIF-5A, eukaryotic initiation factor 5A; ERG, early response gene; hnRNPs, heterogeneous nuclear ribonucleoproteins.

© 2000 The Rockefeller University Press

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