CD8+T cell deficiency impairs control of Epstein-Barr virus and worsens with age in multiple sclerosis

A large body of evidence indicates that infection with the Epstein–Barr virus (EBV) has a role in the pathogenesis of multiple sclerosis (MS).1 We have previously hypothesised that a genetically determined defect in the elimination of EBV-infected B cells by cytotoxic CD8 T cells might predispose to the development of MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system (CNS).1 2 Recently, we have shown that patients with MS have a decreased frequency of CD8 T cells reactive to their own EBV-infected B cells.3 Since 1980, it has been recognised that MS patients have a decreased proportion and number of CD8 T cells in peripheral blood.4 This was initially interpreted as a decrease in CD8 suppressor T cells leading to disinhibition of autoimmune responses but was later attributed to sequestration of CD8 T cells in the CNS. An alternative explanation is that the CD8 T cell deficiency is genetically determined and causes the decreased CD8 T cell response to EBV,3 which allows the accumulation of EBV-infected B cells in the CNS and the consequent development of MS. In the present study, we have used flow cytometry to determine the frequency of CD8 T cells in the blood and its relationship to the EBV-specific T cell response and clinical features of MS. Blood was collected from 64 MS patients and 68 age- and sex-matched healthy subjects after obtaining informed consent. This study was approved by the Royal Brisbane & Women's Hospital …