Evidence for Fas-dependent and Fas-independent mechanisms in the pathogenesis of experimental autoimmune encephalomyelitis

To determine whether Fas or Fas ligand (FasL) plays a role in susceptibilit y to experimental autoimmune encephalomyelitis (EAE), we bred a TCR transge nic mouse specific for the Acl-11 peptide of myelin basic protein to mice w ith inactivating mutations in Fas (lpr) or Fast (gld), Disease induction by peptide immunization in such mice produced similar disease scores, demonst rating that Fas/FasL interactions were not necessary to generate EAE, Howev er, adoptive transfer experiments showed evidence that these interactions c an play a role in the pathogenesis of EAE, shown most dramatically by the a bsence of disease following transfer of cells from a normal myelin basic pr otein TCR transgenic mouse into a Fas-deficient lpr recipient. Furthermore, transfer of cells lacking Fast (gld) into normal or gld recipients gave a diminished disease score. Thus, Fas/FasL interactions can play a role in th e pathogenesis of EAE, but they are not required for disease to occur.