Analysis of CD4 + CD8 + double‐positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions

Summary T cells with a CD4 + CD8 + double‐positive ( DP ) phenotype are present in small numbers in the peripheral blood of healthy humans and may have anti‐viral capacities. Here we investigate numbers and function of DP T cells in patients with relapsing–remitting multiple sclerosis ( MS ), either treatment‐naive or under therapy with natalizumab. Flow cytometry analysis revealed that frequencies of circulating DP T cells in treatment‐naive and natalizumab‐treated MS patients are comparable to healthy controls. These cells have a memory phenotype with cytotoxic potential, express high levels of CD49d and are similarly functional in treatment‐naive as well as natalizumab‐treated MS patients. DP T cells were enriched in the cerebrospinal fluid, but do not invade acutely inflamed MS lesions. In conclusion, DP T cells are functional in MS and may play a role in the immune surveillance of the central nervous system, but do not display functional impairment under natalizumab therapy.