Role of the Th1 and Th17 Pathway in Subacute Sclerosing Panencephalitis

Abstract

Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal disease caused by reactivation of a mutated measles virus in brain tissue. The process of reactivation is yet to be elucidated. In this study, the possible roles of the Th1 (interleukin [IL]-12, interferon [IFN]-γ) and the Th17 axis (IL-23, IL-17, IL-22), particularly of IL-17, in the pathogenesis of SSPE were investigated. Briefly, mononuclear cells from SSPE patients were stimulated using measles virus peptide, and the release of IL-12, IL-23, IL-22, IFN-γ, and IL-17 cytokines was measured using enzyme-linked immunosorbent assay and/or enzyme-linked immunosorbent spot assay (ELISpot). We found that in comparison to the mononuclear cells obtained from healthy donors, cells from SSPE patients exhibited increased levels of IL-12, IL-23, IL-17, IL-22, and IFN-γ cytokines in response to measles virus stimulation. However, the same result was not obtained with cytomegalovirus and phytohemagglutinin. Using flow cytometry, mononuclear cells obtained from SSPE patients and healthy controls were also analyzed for the presence of intracellular IL-17 in response to measles virus stimulation. On stimulation, the number of IL-17-positive cells were found to be higher among mononuclear cells obtained from the patients. In addition, the numbers of IL-17- and IFN-γ-positive cells were significantly increased in SSPE patients. In conclusion, this study demonstrates that both the IL-12/IFN-γ and the IL-23/IL-17/IL-22 pathways are functionally abnormal in SSPE pathogenesis. Targeting these pathways and their specific pro-inflammatory mediator production may provide a new strategy to suppress SSPE development.

Immune alterations in subacute sclerosing panencephalitis reflect an incompetent response to eliminate the measles virus

“…Lower IL-12 secretion in response to MeV vaccine and PPD, and IFN-γ and IL-10 productions to PPD have also provided evidence for alterations in immune response regulation in a previous study [8]. More recently, activated IL-12/IFN-γ and the IL-23/IL-17/IL-22 pathways were reported in SSPE patients [9].…”

“…The decrease in regulatory T cell phenotype and the lower inhibitory NK receptors on CD8 + T cells, and higher activating NK receptors on NK cells indicated also an active state of the immune response possibly caused by the chronic stimulation with viral antigens [19]. A recent report demonstrated increased productions of IL-12, IL-23, IL-17 and IL-22 and higher frequencies of IL-17 and IFN-γ producing cells in response to MeV peptide stimulation in SSPE pointing at both Th1 and Th17 responses [9]. In the present study, production of IL-10 was lower in SSPE compared with both control groups spontaneously and after T cell stimulation.…”

Association of NOD1 and NOD2 Polymorphisms With Susceptibility to Subacute Sclerosing Panencephalitis

“…It is a possibility that subacute sclerosing panencephalitis is the result of a poor cellular immune response. 3,7 The NOD-like receptor (NLR) family includes intracellular proteins that mediate an innate immune response. 8 NOD1 and NOD2 are members of the NLR family.…”