CD83 is up-regulated on the surface of dendritic cells (DCs) during maturation and has been widely used as a marker for mature DCs. Recently, we reported the recombinant expression of the extracellular immunoglobulin domain of human CD83 (hCD83ext). Using this soluble form of CD83, allogeneic as well as specific cytotoxic T lymphocyte proliferation could be blocked in vitro. Here we report the functional analysis of soluble CD83 in vivo, using murine experimental autoimmune encephalomyelitis (EAE) as a model. Strikingly, only three injections of soluble CD83 prevented the paralysis associated with EAE almost completely. In addition, even when the EAE was induced a second time, CD83-treated mice were protected, indicating a long-lasting suppressive effect. Furthermore, soluble CD83 strongly reduced the paralysis in different therapeutic settings. Most important, even when the treatment was delayed until the disease symptoms were fully established, soluble CD83 clearly reduced the paralyses. In addition, also when EAE was induced a second time, soluble CD83-treated animals showed reduced disease symptoms. Finally, hCD83ext treatment almost completely reduced leukocyte infiltration in the brain and in the spinal cord. In summary, this work strongly supports an immunosuppressive role of soluble CD83, thereby indicating its therapeutic potential in the regulation of immune disorders in vivo.
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2 August 2004
Article|
August 02 2004
Prevention and Treatment of Experimental Autoimmune Encephalomyelitis by Soluble CD83
Elisabeth Zinser,
Elisabeth Zinser
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
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Matthias Lechmann,
Matthias Lechmann
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
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Antje Golka,
Antje Golka
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
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Manfred B. Lutz,
Manfred B. Lutz
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
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Alexander Steinkasserer
Alexander Steinkasserer
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
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Elisabeth Zinser
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
Matthias Lechmann
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
Antje Golka
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
Manfred B. Lutz
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
Alexander Steinkasserer
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
Address correspondence to Alexander Steinkasserer, Department of Dermatology, Hartmannstasse 14, University Hospital Erlangen, 91052 Erlangen, Germany. Phone: 49-9131-853-6725; Fax: 49-9131-853- 5799; email: [email protected]
Abbreviations used in this paper: BM-DC, BM-derived DC; EAE, experimental autoimmune encephalomyelitis; GST, glutathione S-transferase; MOG, myelin oligodendrocyte glycoprotein; Pt, pertussis toxin.
Received:
June 13 2003
Accepted:
June 25 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2004
J Exp Med (2004) 200 (3): 345–351.
Article history
Received:
June 13 2003
Accepted:
June 25 2004
Citation
Elisabeth Zinser, Matthias Lechmann, Antje Golka, Manfred B. Lutz, Alexander Steinkasserer; Prevention and Treatment of Experimental Autoimmune Encephalomyelitis by Soluble CD83 . J Exp Med 2 August 2004; 200 (3): 345–351. doi: https://doi.org/10.1084/jem.20030973
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