Barnett and Prineas observed dying OLs in a small subset of brain stem lesions which showed morphological features typically associated with apoptotic cell death; however, only 2% of the apoptotic OLs were stated to be immuno-reactive for activated caspase-334. The authors did put forward however, the challenges of detecting caspase-3 expression in OL in post-mortem tissue due to the potential rapid disappearance of dying cells, or tissue preservation artefacts. This OL pathology was stated to resemble the type III lesions described by Lucchinetti et al.9,35. A concept suggested by Casaccia and Bodekke is that OL death in MS lesions could reflect a continuum of injury mechanisms dependent upon the specific insults and its severity36. We have shown that multiple types of cytotoxic immune cells found in acute lesions, including γδ T cells, activated NK cells37, CD56 + NKG2C + CD4 + T cells38, and CD4 + Th17 cells39 can mediate non-MHC restricted cell-cell contact lethal injury of human adult brain-derived mature OLs in vitro (Fig. 2). In addition, Jamann et al. showed that for CD4 + Th17 cells, OL cytotoxicity was perforin/granzyme-dependent40.
