Progressive multifocal leukoencephalopathy (PML): in vitro cell-mediated immune responses to mitogens and JC virus

Cell-mediated immunity was studied by in vitro tests in seven patients with progressive multifocal leukoencephalopathy (PML). Lymphocyte proliferation in response to mitogenic stimulation was reduced to a variable degree in all patients, indicating a general impairment of cell-mediated immune responsiveness, although mitogen-induced production of the lymphokine migration inhibitory factor (LIF) was normal in most cases. Cell-mediated immunity to JC virus (JCV) was assessed by LIF production in response to JCV antigen. In the six PML patients tested, LIF production with JCV antigen was absent despite the presence of antibody to JCV in serum. This contrasted with positive LIF production in seropositive normal individuals and patients and patients with other diseases. These results provide the first in vitro evidence of a depressed cell-mediated immune response to JCV in patients with PML, and support the hypothesis that PML is accompanied by a selective marked deficiency in cellular response to this virus in association with a general depression of cell-mediated immunity of variable severity.