Differential Susceptibility to Experimental Autoimmune Neuritis in Lewis Rat Strains Is Associated With T-Cell Immunity to Myelin Antigens Wei Zhu, 1 Kejia Zhang, 2,3 Eilhard Mix, 4 Xiaolin Wang, 5,6 Abdu Adem, 7 and Jie Zhu 3,8 * 1 Department of Otorhinolaryngology, the First Hospital, JiLin University, Changchun, China 2 Department of Plastic and Cosmetic Surgery, the First Hospital, JiLin University, Changchun, China 3 Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden 4 Department of Neurology, University of Rostock, Rostock, Germany 5 Department of Surgery, the Affiliated Hospital of Qing Hai University, Xining, China 6 Department of Transplantation, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden 7 Department of Pharmacology, Faculty of Medicine and Health Sciences, United Arab Emirates University, United Arab Emirates 8 Department of Neurology, The First Hospital of Jilin University, Changchun, China Experimental autoimmune neuritis (EAN) is a CD4 1 T- cell-mediated inflammatory demyelinating disease of the peripheral nervous system (PNS) that serves as a model for Guillain-Barre ´ syndrome (GBS) in humans. Various rat strains show different susceptibility to EAN. We exam- ined 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 histo- compatibility class II expression as well as enhanced mi- togenic (phytohemagglutinin-induced) and antigen-spe- cific (P2 peptide 57–81-induced) lymphocyte proliferation compared with the Taconic strain. The Hannover strain also showed increased proinflammatory cytokine (inter- feron-g and tumor necrosis factor-a) 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. V V C 2010 Wiley-Liss, Inc. Key words: autoimmunity; demyelinating disease; peripheral nervous system; cytokines Experimental autoimmune neuritis (EAN) is a widely used animal model of the acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barre ´ syndrome (GBS), an inflammatory autoimmune disease of the pe- ripheral nervous system (PNS) characterized by damage to myelin and axon (Gold et al., 2000; Kieseier et al., 2004). In particular, EAN represents a good model with which to explore the pathogenesis of and test therapeutic strategies for GBS. So far, the immune mechanisms involved in the development of GBS and EAN are not well understood, but an integrated attack of autoreactive myelin-specific T cells and the action of proinflamma- tory cytokines has been supposed to play a pivotal role in the pathogenesis of both diseases (Hartung et al., 1995, 1996; Zhu et al., 1998a; Hughes et al., 2007). Differences in susceptibility to EAN were found between different strains of rats (Hoffman et al., 1980; Zhu et al., 1998b). In general, strains that are susceptible to EAN are also susceptible to experimental autoimmune encephalomyelitis (EAE), an analogous disease of the central nervous system (CNS) that is an animal model Contract grant sponsor: Swedish Medicine Association; Contract grant sponsor: Swedish National Board of Health and Welfare; Contract grant sponsor: Knut and Alice Wallenbergs Foundation. *Correspondence to: Dr. Jie Zhu, Department of Neurobiology, Care Sciences and Society (NOVUM, plan 5), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden SE-141 86. E-mail: jie.zhu@ki.se Received 26 June 2010; Revised 16 September 2010; Accepted 27 September 2010 Published online 22 December 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jnr.22541 Journal of Neuroscience Research 89:448–456 (2011) ' 2010 Wiley-Liss, Inc.