| First Author | Brunn A | Year | 2014 |
| Journal | J Neuropathol Exp Neurol | Volume | 73 |
| Issue | 5 | Pages | 454-66 |
| PubMed ID | 24709684 | Mgi Jnum | J:329107 |
| Mgi Id | MGI:6862461 | Doi | 10.1097/NEN.0000000000000069 |
| Citation | Brunn A, et al. (2014) Costimulatory molecule CD40 is essential for myelin protein 0 peptide 106-125-induced experimental autoimmune neuritis in mice. J Neuropathol Exp Neurol 73(5):454-66 |
| abstractText | Myelin protein 0 peptide 106-125-induced murine experimental autoimmune neuritis (EAN) is a CD4-positive T cell-mediated monophasic axonal inflammatory neuropathy; interferon-gamma 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-gamma 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-kappaB 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. |
