Naslov
Costimulatory Molecule CD40 Is Essential for Myelin Protein 0 Peptide 106-125-Induced Experimental Autoimmune Neuritis in Mice

Autori
Brunn, Anna ; Utermoehlen, Olaf ; Mihelčić, Mirna ; Saupe, Lisa ; Fiocco, Zeno ; Schmidt, Annika ; Carstov, Mariana ; Montesinos-Rongen, Manuel ; Deckert, Martina

Izvornik
Journal of neuropathology and experimental neurology (0022-3069) 73 (2014), 5; 454-466

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CD4 T cells; CD40; costimulatory molecule; experimental autoimmune neuritis; Guillain-Barre syndrome; interferon-gamma

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA