Differential roles of Fas ligand in spontaneous and actively induced autoimmune encephalomyelitis

To determine the roles of Fas/Fas ligand (FasL) in autoimmunity, we studied spontaneous and actively induced autoimmune encephalomyelitis in 541 myelin basic protein-specific T cell receptor transgenic mice. We found that spontaneous autoimmune encephalomyelitis, which was initiated by unidentified microbial factors, was dramatically exacerbated in mice carrying Fas or FasL gene mutation. The exacerbation of autoimmune encephalomyelitis was reflected primarily by an increase in disease incidence and a decrease in spontaneous disease recovery. By contrast, actively induced encephalomyelitis, which was initiated by pertussis toxin, was significantly inhibited by Fas or FasL gene mutation. These results suggest that environmental factors that trigger autoimmune disease may determine not only whether disease will occur but also whether an immune molecule such as FasL will promote or inhibit the autoimmune process.