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Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a risk for natalizumab-treated multiple sclerosis (MS) patients. Here we characterize the JCV-specific T cell responses in healthy donors and natalizumab-treated MS patients to reveal functional differences that may accoun...

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Autores principales: Perkins, Molly R., Ryschkewitsch, Caroline, Liebner, Julia C., Monaco, Maria Chiara G., Himelfarb, Danielle, Ireland, Sara, Roque, Annelys, Edward, Heather L., Jensen, Peter N., Remington, Gina, Abraham, Thomas, Abraham, Jaspreet, Greenberg, Benjamin, Kaufman, Charles, LaGanke, Chris, Monson, Nancy L., Xu, Xiaoning, Frohman, Elliot, Major, Eugene O., Douek, Daniel C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493478/
https://www.ncbi.nlm.nih.gov/pubmed/23144619
http://dx.doi.org/10.1371/journal.ppat.1003014
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author Perkins, Molly R.
Ryschkewitsch, Caroline
Liebner, Julia C.
Monaco, Maria Chiara G.
Himelfarb, Danielle
Ireland, Sara
Roque, Annelys
Edward, Heather L.
Jensen, Peter N.
Remington, Gina
Abraham, Thomas
Abraham, Jaspreet
Greenberg, Benjamin
Kaufman, Charles
LaGanke, Chris
Monson, Nancy L.
Xu, Xiaoning
Frohman, Elliot
Major, Eugene O.
Douek, Daniel C.
author_facet Perkins, Molly R.
Ryschkewitsch, Caroline
Liebner, Julia C.
Monaco, Maria Chiara G.
Himelfarb, Danielle
Ireland, Sara
Roque, Annelys
Edward, Heather L.
Jensen, Peter N.
Remington, Gina
Abraham, Thomas
Abraham, Jaspreet
Greenberg, Benjamin
Kaufman, Charles
LaGanke, Chris
Monson, Nancy L.
Xu, Xiaoning
Frohman, Elliot
Major, Eugene O.
Douek, Daniel C.
author_sort Perkins, Molly R.
collection PubMed
description Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a risk for natalizumab-treated multiple sclerosis (MS) patients. Here we characterize the JCV-specific T cell responses in healthy donors and natalizumab-treated MS patients to reveal functional differences that may account for the development of natalizumab-associated PML. CD4 and CD8 T cell responses specific for all JCV proteins were readily identified in MS patients and healthy volunteers. The magnitude and quality of responses to JCV and cytomegalovirus (CMV) did not change from baseline through several months of natalizumab therapy. However, the frequency of T cells producing IL-10 upon mitogenic stimulation transiently increased after the first dose. In addition, MS patients with natalizumab-associated PML were distinguished from all other subjects in that they either had no detectable JCV-specific T cell response or had JCV-specific CD4 T cell responses uniquely dominated by IL-10 production. Additionally, IL-10 levels were higher in the CSF of individuals with recently diagnosed PML. Thus, natalizumab-treated MS patients with PML have absent or aberrant JCV-specific T cell responses compared with non-PML patients, and changes in T cell-mediated control of JCV replication may be a risk factor for developing PML. Our data suggest further approaches to improved monitoring, treatment and prevention of PML in natalizumab-treated patients.
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spelling pubmed-34934782012-11-09 Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy Perkins, Molly R. Ryschkewitsch, Caroline Liebner, Julia C. Monaco, Maria Chiara G. Himelfarb, Danielle Ireland, Sara Roque, Annelys Edward, Heather L. Jensen, Peter N. Remington, Gina Abraham, Thomas Abraham, Jaspreet Greenberg, Benjamin Kaufman, Charles LaGanke, Chris Monson, Nancy L. Xu, Xiaoning Frohman, Elliot Major, Eugene O. Douek, Daniel C. PLoS Pathog Research Article Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a risk for natalizumab-treated multiple sclerosis (MS) patients. Here we characterize the JCV-specific T cell responses in healthy donors and natalizumab-treated MS patients to reveal functional differences that may account for the development of natalizumab-associated PML. CD4 and CD8 T cell responses specific for all JCV proteins were readily identified in MS patients and healthy volunteers. The magnitude and quality of responses to JCV and cytomegalovirus (CMV) did not change from baseline through several months of natalizumab therapy. However, the frequency of T cells producing IL-10 upon mitogenic stimulation transiently increased after the first dose. In addition, MS patients with natalizumab-associated PML were distinguished from all other subjects in that they either had no detectable JCV-specific T cell response or had JCV-specific CD4 T cell responses uniquely dominated by IL-10 production. Additionally, IL-10 levels were higher in the CSF of individuals with recently diagnosed PML. Thus, natalizumab-treated MS patients with PML have absent or aberrant JCV-specific T cell responses compared with non-PML patients, and changes in T cell-mediated control of JCV replication may be a risk factor for developing PML. Our data suggest further approaches to improved monitoring, treatment and prevention of PML in natalizumab-treated patients. Public Library of Science 2012-11-08 /pmc/articles/PMC3493478/ /pubmed/23144619 http://dx.doi.org/10.1371/journal.ppat.1003014 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Perkins, Molly R.
Ryschkewitsch, Caroline
Liebner, Julia C.
Monaco, Maria Chiara G.
Himelfarb, Danielle
Ireland, Sara
Roque, Annelys
Edward, Heather L.
Jensen, Peter N.
Remington, Gina
Abraham, Thomas
Abraham, Jaspreet
Greenberg, Benjamin
Kaufman, Charles
LaGanke, Chris
Monson, Nancy L.
Xu, Xiaoning
Frohman, Elliot
Major, Eugene O.
Douek, Daniel C.
Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
title Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
title_full Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
title_fullStr Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
title_full_unstemmed Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
title_short Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
title_sort changes in jc virus-specific t cell responses during natalizumab treatment and in natalizumab-associated progressive multifocal leukoencephalopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493478/
https://www.ncbi.nlm.nih.gov/pubmed/23144619
http://dx.doi.org/10.1371/journal.ppat.1003014
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