In aggressive disease forms, these T cells are frequently localized close to OLGs and axons and express granzyme B .
OLGs may withstand limited or sublytic complement ttack by shedding membrane areas that contain C5b-9 complexes .
Immunohistochemical analysis revealed increased Fas expression on OLGs on MS lesions; furthermore, the microglia and lymphocytes in the lesions showed intense staining for FasL .
TNF-[alpha] can induce both apoptotic and necrotic death of OLGs. Caspase 1 and caspase 3 inhibition protects OLGs against TNF-[alpha]-induced apoptosis [38-41].
IFN-[gamma] can also be cytotoxic to OLGs in culture by modulating the cellular response to injury; these responses involve up-regulation of Fas expression [30,32-33] (Figure 2).
In MS, demyelination is accompanied by extensive destruction and loss of OLGs .
The presence of this mRNA was correlated with increased immunostaining of caspase 1 in MS brains and OLGs. Caspase 1-deficient mice develop a less severe form of EAE .
As assessed by the TUNEL method, more than 50 percent of OLGs differentiated in the absence of serum growth factor for 72 h in vitro are apoptotic.
Upstream signaling studies showed that C5b-9 induced strong PI3-K/Akt activities in OLGs; these activities in turn phosphorylated Bcl-2-associated death promoter (Bad).
Deposition of C5b-9 has also been shown in Pattern II but not Pattern III lesions where apoptotic OLGs are prevalent .
ROLE OF OLG APOPTOSIS IN MULTIPLE SCLEROSIS AND EAE
We also analyzed the effect of C5 on OLG apoptosis during EAE in C5-d mice .