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Open Access 01-04-2017 | Original Paper

Differences in T cell cytotoxicity and cell death mechanisms between progressive multifocal leukoencephalopathy, herpes simplex virus encephalitis and cytomegalovirus encephalitis

Authors: Susanne Laukoter, Helmut Rauschka, Anna R. Tröscher, Ulrike Köck, Etsuji Saji, Kurt Jellinger, Hans Lassmann, Jan Bauer

Published in: Acta Neuropathologica | Issue 4/2017

Abstract

During the appearance of human immunodeficiency virus infection in the 1980 and the 1990s, progressive multifocal leukoencephalopathy (PML), a viral encephalitis induced by the JC virus, was the leading opportunistic brain infection. As a result of the use of modern immunomodulatory compounds such as Natalizumab and Rituximab, the number of patients with PML is once again increasing. Despite the presence of PML over decades, little is known regarding the mechanisms leading to death of infected cells and the role the immune system plays in this process. Here we compared the presence of inflammatory T cells and the targeting of infected cells by cytotoxic T cells in PML, herpes simplex virus encephalitis (HSVE) and cytomegalovirus encephalitis (CMVE). In addition, we analyzed cell death mechanisms in infected cells in these encephalitides. Our results show that large numbers of inflammatory cytotoxic T cells are present in PML lesions. Whereas in HSVE and CMVE, single or multiple appositions of CD8⁺ or granzyme-B⁺ T cells to infected cells are found, in PML such appositions are significantly less apparent. Analysis of apoptotic pathways by markers such as activated caspase-3, caspase-6, poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) showed upregulation of caspase-3 and loss of caspase-6 from mitochondria in CMVE and HSVE infected cells. Infected oligodendrocytes in PML did not upregulate activated caspase-3 but instead showed translocation of PARP-1 from nucleus to cytoplasm and AIF from mitochondria to nucleus. These findings suggest that in HSVE and CMVE, cells die by caspase-mediated apoptosis induced by cytotoxic T cells. In PML, on the other hand, infected cells are not eliminated by the immune system but seem to die by virus-induced PARP and AIF translocation in a type of cell death defined as parthanatos.

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Title: Differences in T cell cytotoxicity and cell death mechanisms between progressive multifocal leukoencephalopathy, herpes simplex virus encephalitis and cytomegalovirus encephalitis
Authors: Susanne Laukoter
Helmut Rauschka
Anna R. Tröscher
Ulrike Köck
Etsuji Saji
Kurt Jellinger
Hans Lassmann
Jan Bauer
Publication date: 01-04-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 4/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1642-1

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Springer Medicine

Differences in T cell cytotoxicity and cell death mechanisms between progressive multifocal leukoencephalopathy, herpes simplex virus encephalitis and cytomegalovirus encephalitis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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