Figure 9.

Programmed death 1 (PD‐1) on CD8⁺ CD57⁺ regulates the response to Epstein–Barr virus (EBV) and the reactivation of the virus in the central nervous system (CNS) of patients with multiple sclerosis (MS). In patients with MS during remission, the high expression of PD‐1 in CD8⁺ CD57⁺ T cells suggests a dysfunctional, reduced cytotoxic response that allows MS‐associated viruses such as EBV to persist in the CNS and favours persistent inflammation with tissue damage and consequent relapses. Newly activated CD8⁺ CD57⁺ T cells might be induced to clear virus‐infected targets in active MS but the repeated antigenic stimulation and inflammatory cytokines contribute to up‐regulation of PD‐1 with a decrease of effector function.