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J Clin Invest. 2000 Jan;105(2):223-31.

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

Author information

1
Department of Microbiology-Immunology, Interdepartmental Immunobiology Center, Northwestern University Medical School and the Northwestern University Institute for Neuroscience, Chicago, Illinois 60611, USA.

Abstract

PLP139-51-induced experimental autoimmune encephalomyelitis (R-EAE) displays a relapsing-remitting paralytic course in female SJL mice. We investigated the role of apoptosis/activation-induced cell death (AICD) in the spontaneous recovery from acute disease. Clinical EAE was significantly enhanced in Fas (CD95/APO-1)-deficient SJL lpr/lpr mice, which displayed significantly increased mean peak clinical scores, reduced remission rates, and increased mortality when compared with their SJL +/lpr littermates. PLP139-151-specific proliferative responses were fairly equivalent in the 2 groups, but draining lymph node T cells from SJL lpr/lpr mice produced dramatically increased levels of IFN-gamma. Central nervous system (CNS) Fas and FasL mRNA levels in wild-type SJL (H-2(s)) mice peaked just before spontaneous disease remission and gradually declined as disease remitted. We applied the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay 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 inflammation: the acute, peak, and relapse time points. Significantly fewer apoptotic cells were observed at preclinical and remission time points. Collectively, these findings indicate that Fas-mediated apoptosis/AICD plays a major role in the spontaneous remission after the initial acute inflammatory episode and represents an important intrinsic mechanism in regulation of autoimmune responses.

PMID:
10642601
PMCID:
PMC377433
DOI:
10.1172/JCI8561
[Indexed for MEDLINE]
Free PMC Article

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