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 healthy donors (HD), 6 human immunodeficiency virus‐1 (HIV‐1)‐infected patients without PML (HIV), 4 HIV‐1‐negative patients with PML (PML), and 8 HIV‐1‐positive patients with PML (HIV/PML). As antigens, recombinant virus‐like particles of the major structural protein VP1 (VP1‐VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1‐VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon‐γ (IFN‐γ) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin‐10 (IL‐10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1‐VLP was slightly 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.