PRF1 and tick-borne encephalitis: Since activated TBEV-specific CD8+ T cells show upregulation of perforin and granzyme B [104] and CD8+ granzyme B+ T cells have been found in the brain tissue of fatal TBE cases associated with neuronal damage [168], indeed they may contribute to the pathogenesis, although uncontrolled virus replication may result also in a worse outcome of disease.