AUTOREACTIVE T-CELL RESPONSES AND CYTOKINE PATTERNS REFLECT RESISTANCE TO EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS IN WISTAR FURTH RATS

Various mouse and rat strains show different susceptibilities to exper imental autoimmune myasthenia gravis (EAMG) that can be induced by imm unization with acetylcholine receptor (AChR) and Freund's complete adj uvant, and represents a model for the antibody-mediated myasthenia gra vis in humans. We examined AChR-induced B and T cell responses and cyt okine mRNA expression to study the mechanisms behind susceptibility to EAMG in Lewis rats and resistance in Wistar Furth (WF) rats. Both str ains had similarly elevated concentrations and affinities of serum ant i-AChR antibodies, and no difference between the two strains for frequ encies of cells in lymphoid organs expressing mRNA of the B cell stimu lating cytokine interleukin-4 was found. In contrast, T cell responses to AChR measured by proliferation and by enumeration of interferon-ga mma-expressing cells at both mRNA and protein level were lower in the resistant WF rats. This strain showed, instead, an up-regulation of th e anti-inflammatory transforming growth factor-beta. Strain-related di fferences in the susceptibility to actively induced EAMG are thus rela ted to quantitative differences in distribution between pro-inflammato ry and anti-inflammatory cytokines.