RESISTANCE AND SUSCEPTIBILITY TO EXPERIMENTAL AUTOIMMUNE NEURITIS IN SPRAGUE-DAWLEY AND LEWIS RATS CORRELATE WITH DIFFERENT LEVELS OF AUTOREACTIVE T-CELL AND B-CELL RESPONSES TO MYELIN ANTIGENS

Experimental autoimmune neuritis (EAN) is a CD4(+) T cell-mediated, in flammatory demyelinating disease of the peripheral nervous system (PNS ) that serves as a model for Guillain-Barre syndrome (GBS) in humans. Various mouse and rat strains show different susceptibilities to EAN t hat can be induced by immunization with bovine PNS myelin (BPM) + Freu nd's complete adjuvant (FCA), We examined PNS-induced T and B cell res ponses and cytokine protein production as well as mRNA expression to s tudy the mechanisms behind susceptibility to EAN in Lewis rats and res istance in Sprague-Dawley (SD) rats. Lewis rats with EAN have elevated PNS myelin-reactive interferon-gamma (IFN-gamma) production, TNF-alph a mRNA expression, and increased B cell responses to PNS myelin antige ns, but low PNS myelin-reactive transforming growth factor-beta (TGF-b eta) and interleukin (IL)-10 mRNA expression in lymph node mononuclear cells (MNC). In contrast, resistance to EAN in SD rats is associated with reduced RPM and P2 peptide-reactive IFN-gamma production, TNF-alp ha mRNA expression, and suppressed B cell responses to PNS myelin anti gens as well as up-regulation of TGF-beta and IL-10 mRNA expression. R esistance to EAN is also associated with low-grade inflammation or abs ence of histological evidence of EAN, These results suggest that diffe rential autoreactive T and B cells responses to PNS myelin antigens ar e strain specific, and the susceptibility to EAN is related to quantit ative rather than qualitative differences in distribution between proi nflammatory and anti-inflammatory cytokines, (C) 1998 Wiley-Liss, Inc.