JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the polyomavirus JC (JCV) within a setting of immunosuppression, The nature of the immune r esponse that contains replication of this virus is unknown. We have explore d JCV-specific cellular immune responses in patients with PML and control s ubjects. JCV antigen-stimulated peripheral blood mononuclear cells (PBMC) o f four human immunodeficiency virus (HIV)-infected patients who were surviv ors of PML and one HIV-uninfected patient recently diagnosed with PML lysed autologous B-lymphoblastoid cell lines expressing either the JCV T regulat ory protein or the VP1 major capsid protein. This lysis was mediated by CD8 (+) T lymphocytes and was major histocompatibility complex class I restrict ed. These cells were therefore cytotoxic T lymphocytes (CTL). JCV-specific CTL could not be detected in PBMC of three HIV-infected PML patients who ha d progressive neurologic disease and an eventual fatal outcome. These data suggest that the JCV-specific cellular immune response may play a crucial r ole in the containment of PML. This finding may also prove useful as a favo rable prognostic marker in the clinical management of these patients.