Brunn, Anna, Utermoehlen, Olaf, Mihelcic, Mirna ORCID: 0000-0002-8241-1721, Saupe, Lisa, Fiocco, Zeno, Schmidt, Annika, Carstov, Mariana, Montesinos-Rongen, Manuel and Deckert, Martina (2014). Costimulatory Molecule CD40 Is Essential for Myelin Protein 0 Peptide 106Y125YInduced Experimental Autoimmune Neuritis in Mice. J. Neuropathol. Exp. Neurol., 73 (5). S. 454 - 467. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1554-6578

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Abstract

Myelin protein 0 peptide 106-125-induced murine experimental autoimmune neuritis (EAN) is a CD4-positive T cell-mediated monophasic axonal inflammatory neuropathy; interferon- is the key proinflammatory mediator. Experimental autoimmune neuritis is well suited for elucidating pathogenetic mechanisms underlying human acute axonal Guillain-Barre syndrome. Here, the functional role of the costimulatory molecule CD40 was defined by characterization of EAN in CD40-deficient mice. In contrast to immunized C57BL/6 mice, CD40-deficient mice were resistant to EAN owing to impaired priming of CD4-positive T-effector cells. To determine whether CD40 is a suitable candidate for the treatment of EAN, we administered monoclonal anti-CD40 antibody either before immunization or upon onset of neurologic signs. Prophylactic anti-CD40 treatment completely abolished CD4-positive T-cell priming. Therapeutic application of anti-CD40 prevented full activation of CD4-positive T cells that were in the process of priming and suppressed production of interferon- in peripheral lymph nodes, spleen, and serum, and of interleukin-6, interleukin-12p40, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, which are associated with activation of the nuclear factor-B signaling pathway. This resulted in enhanced recovery by early generation of CD25-positive, Foxp3-positive, CD4-positive regulatory T cells. Thus, these experiments highlight the crucial role of CD40 as an important costimulatory molecule in EAN and suggest that it has potential as a therapeutic target in human neuritis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brunn, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Utermoehlen, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mihelcic, MirnaUNSPECIFIEDorcid.org/0000-0002-8241-1721UNSPECIFIED
Saupe, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fiocco, ZenoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carstov, MarianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montesinos-Rongen, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deckert, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-439373
DOI: 10.1097/NEN.0000000000000069
Journal or Publication Title: J. Neuropathol. Exp. Neurol.
Volume: 73
Number: 5
Page Range: S. 454 - 467
Date: 2014
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 1554-6578
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GUILLAIN-BARRE-SYNDROME; EXPERIMENTAL ALLERGIC NEURITIS; MURINE TOXOPLASMA ENCEPHALITIS; LEISHMANIA-MAJOR AMASTIGOTES; DEPENDENT KILLING MECHANISM; VASCULAR ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; T-CELLS; INTERFERON-GAMMA; LEWIS RATSMultiple languages
Clinical Neurology; Neurosciences; PathologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43937

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