Although a case report suggested the central role of polyfunctional CD4 T cells in natalizumab-associated PML-IRIS, CD4 T cells do not usually infiltrate the CNS parenchyma in HIV-infected patients experiencing PML-IRIS but remain sequestrated in the perivascular vicinity while CD8 T cells penetrate the parenchyma and interact with JCV-infected oligodendrocytes (10, 47). This evidence concerns the gene CD8A and progressive multifocal leukoencephalopathy.