Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation

Abstract Cytomegalovirus (CMV) is a latent virus which causes chronic activation of the immune system. Here, we demonstrate that cytotoxic and pro-inflammatory CD4+CD28null T cells are only present in CMV seropositive donors and that CMV-specific Immunoglobulin (Ig) G titers correlate with the perce...

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Autores principales:	Marjan Vanheusden, Bieke Broux, Suzanne P. M. Welten, Liesbet M. Peeters, Eleni Panagioti, Bart Van Wijmeersch, Veerle Somers, Piet Stinissen, Ramon Arens, Niels Hellings
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3fd87ea4885746a9880b7294e7de70e8
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spelling	oai:doaj.org-article:3fd87ea4885746a9880b7294e7de70e82021-12-02T15:06:23ZCytomegalovirus infection exacerbates autoimmune mediated neuroinflammation10.1038/s41598-017-00645-32045-2322https://doaj.org/article/3fd87ea4885746a9880b7294e7de70e82017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00645-3https://doaj.org/toc/2045-2322Abstract Cytomegalovirus (CMV) is a latent virus which causes chronic activation of the immune system. Here, we demonstrate that cytotoxic and pro-inflammatory CD4+CD28null T cells are only present in CMV seropositive donors and that CMV-specific Immunoglobulin (Ig) G titers correlate with the percentage of these cells. In vitro stimulation of peripheral blood mononuclear cells with CMVpp65 peptide resulted in the expansion of pre-existing CD4+CD28null T cells. In vivo, we observed de novo formation, as well as expansion of CD4+CD28null T cells in two different chronic inflammation models, namely the murine CMV (MCMV) model and the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis (MS). In EAE, the percentage of peripheral CD4+CD28null T cells correlated with disease severity. Pre-exposure to MCMV further aggravated EAE symptoms, which was paralleled by peripheral expansion of CD4+CD28null T cells, increased splenocyte MOG reactivity and higher levels of spinal cord demyelination. Cytotoxic CD4+ T cells were identified in demyelinated spinal cord regions, suggesting that peripherally expanded CD4+CD28null T cells migrate towards the central nervous system to inflict damage. Taken together, we demonstrate that CMV drives the expansion of CD4+CD28null T cells, thereby boosting the activation of disease-specific CD4+ T cells and aggravating autoimmune mediated inflammation and demyelination.Marjan VanheusdenBieke BrouxSuzanne P. M. WeltenLiesbet M. PeetersEleni PanagiotiBart Van WijmeerschVeerle SomersPiet StinissenRamon ArensNiels HellingsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marjan Vanheusden Bieke Broux Suzanne P. M. Welten Liesbet M. Peeters Eleni Panagioti Bart Van Wijmeersch Veerle Somers Piet Stinissen Ramon Arens Niels Hellings Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
description	Abstract Cytomegalovirus (CMV) is a latent virus which causes chronic activation of the immune system. Here, we demonstrate that cytotoxic and pro-inflammatory CD4+CD28null T cells are only present in CMV seropositive donors and that CMV-specific Immunoglobulin (Ig) G titers correlate with the percentage of these cells. In vitro stimulation of peripheral blood mononuclear cells with CMVpp65 peptide resulted in the expansion of pre-existing CD4+CD28null T cells. In vivo, we observed de novo formation, as well as expansion of CD4+CD28null T cells in two different chronic inflammation models, namely the murine CMV (MCMV) model and the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis (MS). In EAE, the percentage of peripheral CD4+CD28null T cells correlated with disease severity. Pre-exposure to MCMV further aggravated EAE symptoms, which was paralleled by peripheral expansion of CD4+CD28null T cells, increased splenocyte MOG reactivity and higher levels of spinal cord demyelination. Cytotoxic CD4+ T cells were identified in demyelinated spinal cord regions, suggesting that peripherally expanded CD4+CD28null T cells migrate towards the central nervous system to inflict damage. Taken together, we demonstrate that CMV drives the expansion of CD4+CD28null T cells, thereby boosting the activation of disease-specific CD4+ T cells and aggravating autoimmune mediated inflammation and demyelination.
format	article
author	Marjan Vanheusden Bieke Broux Suzanne P. M. Welten Liesbet M. Peeters Eleni Panagioti Bart Van Wijmeersch Veerle Somers Piet Stinissen Ramon Arens Niels Hellings
author_facet	Marjan Vanheusden Bieke Broux Suzanne P. M. Welten Liesbet M. Peeters Eleni Panagioti Bart Van Wijmeersch Veerle Somers Piet Stinissen Ramon Arens Niels Hellings
author_sort	Marjan Vanheusden
title	Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
title_short	Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
title_full	Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
title_fullStr	Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
title_full_unstemmed	Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
title_sort	cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3fd87ea4885746a9880b7294e7de70e8
work_keys_str_mv	AT marjanvanheusden cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT biekebroux cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT suzannepmwelten cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT liesbetmpeeters cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT elenipanagioti cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT bartvanwijmeersch cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT veerlesomers cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT pietstinissen cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT ramonarens cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation AT nielshellings cytomegalovirusinfectionexacerbatesautoimmunemediatedneuroinflammation
_version_	1718388443792277504

Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation

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