Mechanism of γδ T cell-induced human oligodendrocyte cytotoxicity: relevance to multiple sclerosis

Role of the innate immune system in the pathogenesis of multiple sclerosis

“…Gamma-delta T cells are present in MS lesions (Selmaj et al, 1991), and are expanded by glial cells (Freedman et al, 1997b). They may lyse oligodendrocytes (Freedman et al, 1991), through a mechanism that involves either heat-shock proteins expressed by oligodendrocytes (Freedman et al, 1997a), or release of perforin or interaction between Fas and Fas ligand (Zeine et al, 1998), or via NKGD2-ligand interaction (Saikali et al, 2007). In conclusion, the gamma-delta T cell population increases in MS patients with “active” or progressive disease, and might contribute to disease pathology by exerting a direct cytotoxic effect on oligodendrocytes.…”

Importance of oligodendrocyte protection, BBB breakdown and inflammation for remyelination

“…Interleukin-2 (IL-2)-mediated activation of NK cells may occur in the inflammatory environment of active MS lesions and could bypass protective effects of self-MHC class I molecules that may be expressed on OLs [35]. γδ T cells have been implicated in the pathogenesis of MS [36] and are cytotoxic toward OL via perforin [37]. γδ T and NK cells interact with OL via NKG2D receptor and a corresponding ligand expressed by OL and mediate cell death via cell lysis or by induction of apoptosis.…”

Multiple Sclerosis and Central Nervous System Demyelination

“…Cultured human OLs have been shown to be efficiently lysed in a dose-dependent manner by human / T cells, although such an effect was not restricted to this cell type [41]. This effect is predominantly mediated through the perforin/granzyme system [42]. Members of the heat shock family of molecules are suggested to be recognition targets of these T cells.…”