© 2014 Mary Ann Liebert, Inc.Subacute sclerosing panencephalitis (SSPE) is caused by a persistent measles virus infection. Regulatory mechanisms can be responsible for a failure of immunosurveillance in children with SSPE. In this study, peripheral blood cells of 71 patients with SSPE and 57 children with other diseases were compared phenotypically. The proportions of CD4+, CD8+ T, and NK cells were homogenous, whereas total CD3+ T and Treg (CD4+CD25+CD152+) cells were decreased in patients with SSPE. The proportion of CD8+ T cells expressing the inhibitory NKG2A+ receptor was also decreased (1.7%±1.7% vs. 2.6%±1.9%, p=0.007) in patients with SSPE, whereas the proportion of NK cells expressing activating NKG2C was increased compared with the control group (30.0%±17.3% vs. 22.2%±17.0%, p=0.039). The decrease in the number of cells with regulatory phenotype, the lower presence of the inhibitory NK receptors on CD8+ cells, and higher activating NK receptors on NK cells in SSPE indicate an upregulation of these cell types that favors their response. This state of active immune response may be caused by chronic stimulation of viral antigens leading to altered regulatory pathways.