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Figure 3. Schematic flow chart depicting the possible mechanism for GrB-mediated activated T cells supernatant-induced neuronal damage. CD3/CD28 activated T cells release GrB into the supernatants. GrB induces neurotoxicity by both perforin-dependent or -independent mechanisms. As for the latter, GrB activates PTX-sensitive Gi-coupled receptors by either direct binding, or by cleaved fragments binding or by direct cleavage. The activation of Gi-coupled receptor then results in decreased cAMP levels and elevated intracellular calcium levels, which may induce caspase-3 activation, leading to neuronal apoptosis. It is likely that oxidative stress also participates in the neurotoxicity, and it is upstream of caspase activation.
