Cellular and humoral immune response in progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV-specific cellular and humoral immune response in 7 heal thy donors (HD), 6 human immunodeficiency virus-1 (HIV-1)-infected patients without PML (HIV), 4 HTV-1-negative patients with PML (PML), and 8 HIV-1-p ositive patients with PML (HIV/PML). As antigens, recombinant virus-like pa rticles of the major structural protein VP1 (VP1-VLP) of JCV, tetanus toroi d (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1-V LP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon-gamma (IFN-gamma) w as reduced in PML, in HIV/PML, and in HIV patients. The production of inter leukin-10 (IL-10), however, was elevated in HIV/PML patients. Neither proli feration nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1-VLP was slightl y elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1-type T-helper cell function of cell-mediated immunity .