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

Abstract

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.

Developmental immunotoxicity investigations in the SD rat following pre- and post-natal exposure to cyclosporin

“…Cyclosporin-induced autoimmunity, however, resembles T cell mediated scleroderma, and would not necessarily result in an increase in autoantibodies. Furthermore, not all strains of rat are sensitive to this effect (Barendrecht et al, 2002) and autoimmunity has yet to be demonstrated in the Sprague Dawley strain (Zhu et al, 1998).…”