Autoreactive T cell responses and cytokine patterns reflect resistance to experimental autoimmune myasthenia gravis in Wistar Furth rats

Abstract

Various mouse and rat strains show different susceptibilities to experimental autoimmune myasthenia gravis (EAMG) that can be induced by immunization with acetylcholine receptor (AChR) and Freund's complete adjuvant, and represents a model for the antibody-mediated myasthenia gravis in humans. We examined AChR-induced B and T cell responses and cytokine mRNA expression to study the mechanisms behind susceptibility to EAMG in Lewis rats and resistance in Wistar Furth (WF) rats. Both strains had similarly elevated concentrations and affinities of serum anti-AChR antibodies, and no difference between the two strains for frequencies of cells in lymphoid organs expressing mRNA of the B cell stimulating cytokine interleukin-4 was found. In contrast, T cell responses to AChR measured by proliferation and by enumeration of interferon-gamma-expressing cells at both mRNA and protein level were lower in the resistant WF rats. This strain showed, instead, an up-regulation of the anti-inflammatory transforming growth factor-beta. Strain-related differences in the susceptibility to actively induced EAMG are thus related to quantitative differences in distribution between pro-inflammatory and anti-inflammatory cytokines.