Fas-mediated apoptosis in clinical remissions of relapsing experimental autoimmune encephalomyelitis

PLP139-51-induced experimental autoimmune encephalomyelitis (R-EAE) display s a relapsing-remitting paralytic course in female SJL mice. We investigate d the role of apoptosis/activation-induced cell death (AICD) in the spontan eous recovery from acute disease. Clinical EAE was significantly enhanced i n Fas (CD95/APO-1)-deficient SJL lpr/lpr mice, which displayed significantl y increased mean peak clinical scores, reduced remission rates, and increas ed mortality when compared with their SJL +/lpr Littermates. PLP139-151-spe cific proliferative responses were fairly equivalent in the 2 groups, but d raining lymph node T cells from SJL lpr/lpr mice produced dramatically incr eased levels of IFN-gamma. Central nervous system (CNS) Fas and Fast mRNA l evels in wild-type SJL (H-2(S)) mice peaked just before spontaneous disease remission and gradually declined as disease remitted. We applied the termi nal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) as say to detect apoptosis in situ in spinal cords of mice at various clinical stages of EAE. Most TUNEL+ cells were found during active periods of infla mmation: the acute, peak, and relapse time points. Significantly fewer apop totic cells were observed at preclinical and remission time points. Collect ively, these findings indicate that Fas-mediated apoptosis/AICD plays a maj or role in the spontaneous remission after the initial acute inflammatory e pisode and represents an important intrinsic mechanism in regulation of aut oimmune responses.