Cell death during autoimmune demyelination: effector but not target cells are eliminated by apoptosis.

The Fas and FasL apoptotic pathway was investigated by protein immunohistochemistry, flow cytometry, and reverse transcriptase-PCR analysis to assess whether it is involved in the elimination of target and/or effector cells from the central nervous system (CNS) during adoptively transferred chronic relapsing experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. In addition to Fas and FasL, we studied Bax, an intracellular protein of the apoptotic cascade, the Bax antagonist and anti-apoptotic molecule Bcl-2, and DNA fragmentation, the final step in the apoptotic pathway. Infiltrating CD4+ T cells and parenchymal microglia expressed Fas, FasL, and Bax, and about half of these cells showed DNA fragmentation, a combination indicative of ongoing apoptosis. Using flow cytometry and reverse transcriptase-PCR, a positive correlation was seen between disease activity and up-regulation of the Fas system; in fact, Fas and FasL were expressed at low levels at the onset ...