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.

• Authors: J Zhu, L P Zou, M Bakhiet, E Mix
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 54 Issue 3 Pg. 373-81 (Nov 01 1998) ISSN: 0360-4012 [Print] United States
• PMID: 9819142 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Immunoglobulin G
• Myelin P2 Protein
• Phytohemagglutinins
• Receptors, Cholinergic

Topics

• Animals
• B-Lymphocytes (immunology, metabolism)
• Body Weight
• Cytokines (genetics)
• Disease Susceptibility
• Immunoglobulin G (immunology)
• In Situ Hybridization
• Lymph Nodes (immunology, metabolism)
• Macrophages (metabolism)
• Male
• Myelin P2 Protein (immunology)
• Myelin Sheath (immunology)
• Neuritis, Autoimmune, Experimental (etiology, immunology)
• Phytohemagglutinins (pharmacology)
• Rats
• Rats, Inbred Lew
• Rats, Sprague-Dawley
• Receptors, Cholinergic (immunology)
• Sciatic Nerve (immunology, pathology)
• T-Lymphocytes (immunology, metabolism)