Resistance and susceptibility to experimental autoimmune neuritis in Sprague-Dawley and Lewis rats correlate with different levels of autoreactive T and B cell responses to myelin antigens.
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 mouse and rat strains show different susceptibilities to EAN that can be induced by immunization with bovine PNS myelin (BPM) + Freund's complete adjuvant (FCA). We examined PNS-induced T and B cell responses and cytokine protein production as well as mRNA expression to study the mechanisms behind susceptibility to EAN in Lewis rats and resistance in Sprague-Dawley (SD) rats. Lewis rats with EAN have elevated PNS myelin-reactive interferon-gamma (IFN-gamma) production, TNF-alpha mRNA expression, and increased B cell responses to PNS myelin antigens, but low PNS myelin-reactive transforming growth factor-beta (TGF-beta) and interleukin (IL)-10 mRNA expression in lymph node mononuclear cells (MNC). In contrast, resistance to EAN in SD rats is associated with reduced BPM and P2 peptide-reactive IFN-gamma production, TNF-alpha mRNA expression, and suppressed B cell responses to PNS myelin antigens as well as up-regulation of TGF-beta and IL-10 mRNA expression. Resistance to EAN is also associated with low-grade inflammation or absence of histological evidence of EAN. These results suggest that differential autoreactive T and B cells responses to PNS myelin antigens are strain specific, and the susceptibility to EAN is related to quantitative rather than qualitative differences in distribution between proinflammatory and anti-inflammatory cytokines.
Zhu
J
J
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Jie.Zhu@cnsf.ki.se
Zou
L P
LP
Bakhiet
M
M
Mix
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001835:Body Weight; D016207:Cytokines / Q000235:genetics; D004198:Disease Susceptibility; D007074:Immunoglobulin G / Q000276:immunology; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D018996:Myelin P2 Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000276:immunology; D012584:Sciatic Nerve / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D007074:Immunoglobulin G; D018996:Myelin P2 Protein; D010835:Phytohemagglutinins; D011950:Receptors, Cholinergic