JC virus detection and JC virus-specific immunity in natalizumab-treated Multiple Sclerosis patients

Background: The use of natalizumab in multiple sclerosis (MS) may favour JC virus reactivation; this phenomenon is usually asymptomatic but can, albeit rarely, evolve into frank progressive multifocal leucoencephalopathy (PML). Methods: JCV-specific CD8+ T lymphocytes were evaluated by flow cytometry over a 24-month period in 24 natalizumab-treated MS patients in whom JCV DNA was or was not detected in blood using quantitative real-time polymerase chain reaction; all these cases were asymptomatic. Results: Perforin-and grazymes-containing VP-1-specific CD8+ T lymphocytes were reduced whereas CD107a expressing cells were increased in JCV positive patients, suggesting an active degranulation of these cells; naive CD8+ T lymphocytes were also decreased whereas memory cells were increased in patients in whom JCV reactivation was observed. Conclusion: The presence of a CD8+ T lymphocyte-mediated effector immune response offers a greater insight into reactivation of JCV and its clinical sequelae, and may help the monitoring of patients on natalizumab therapy.