Fas/Fas ligand pathway, apoptosis, and clonal anergy involved in systemic acetylcholine receptor T cell epitope tolerance

The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell epitope, alpha 146-162 peptide-induced tolerance in experimental my asthenia gravis were examined. CD4 cells are the prime target for alpha 146 -162 peptide-induced tolerance. The expression of CD69, Fas, and B7.2 molec ules on AChR-immune lymphocytes was enhanced within 4-12 h after tolerance induction. A high dose of alpha 146-162 peptide in IFA failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice d eficient in Fas and Fas ligand, respectively. A high dose of alpha 146-162 peptide in IFA in AChR-immunized mice induced apoptosis of BV6 cells. Furth er, reconstitution of IL-2 in vitro-recovered alpha 146-161 peptide toleriz ed T cell proliferation, IFN-gamma, and IL-10 production, The findings impl icate the possible role of Fas-/Fas ligand-mediated apoptosis and the resul ting clonal anergy as the mechanisms of high dose AChR alpha 146-162 peptid e-induced tolerance on CD4 cells.