Differential susceptibility to experimental autoimmune neuritis in Lewis rat strains is associated with T-cell immunity to myelin antigens

• Published in: Journal of neuroscience research 2011-03, Vol.89 (3), p.448-456
• Main Authors: Zhu, Wei, Zhang, Kejia, Mix, Eilhard, Wang, Xiaolin, Adem, Abdu, Zhu, Jie
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animal models; Animals; Antigens - immunology; autoimmunity; Cell Proliferation; Cells, Cultured; Culture Media - chemistry; cytokines; Cytokines - metabolism; demyelinating disease; Disease Models, Animal; Disease Susceptibility; Lymph Nodes - pathology; Macrophages - immunology; Male; Medicin och hälsovetenskap; Myelin Sheath - immunology; Neuritis, Autoimmune, Experimental - immunology; Neuritis, Autoimmune, Experimental - pathology; peripheral nervous system; Rats; Rats, Inbred Lew; Sciatic Nerve - pathology; Species Specificity; Statistics, Nonparametric; T-Lymphocytes - immunology
• ISSN: 0360-4012; 1097-4547; 1097-4547
• DOI: 10.1002/jnr.22541

Experimental autoimmune neuritis (EAN) is a CD4+ T‐cell‐mediated inflammatory demyelinating disease of the peripheral nervous system (PNS) that serves as a model for Guillain‐Barré syndrome (GBS) in humans. Various rat strains show different susceptibility to EAN. We examined PNS myelin‐induced T‐ and B‐cell responses and cytokine production in order to explore the mechanisms behind different EAN susceptibility in the three Lewis rat strains, Hannover, Charles River, and Taconic. Lewis rats of Hannover and Charles River strains exhibited a higher susceptibility to EAN than Lewis rats of the Taconic strain. The higher susceptibility was associated with increased inflammatory cell infiltrates and major histocompatibility class II expression as well as enhanced mitogenic (phytohemagglutinin‐induced) and antigen‐specific (P2 peptide 57–81‐induced) lymphocyte proliferation compared with the Taconic strain. The Hannover strain also showed increased proinflammatory cytokine (interferon‐γ and tumor necrosis factor‐α) production in the PNS. Cross‐cultures of T cells and macrophages from Hannover and Taconic rats revealed that the Hannover rats exerted the strongest priming function of T cells. In contract, the P2 peptide‐induced antibody production was not different among the three Lewis rat strains. In conclusion, the differential susceptibility to EAN of Lewis rat strains is correlated primarily with T‐cell immunity to myelin antigens. © 2010 Wiley‐Liss, Inc.