Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.

In multiple sclerosis (MS), treatment with the monoclonal antibody natalizumab effectively reduces the formation of acute lesions in the central nervous system (CNS). Natalizumab binds the integrin very late antigen (VLA)-4, expressed on the surface of immune cells, and inhibits VLA-4 dependent tran...

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Autores principales:	Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Annette Bang Oturai, Per Soelberg Sørensen, Helle Bach Søndergaard, Finn Sellebjerg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50b0ce6a02984f2e9ac4ed10fcb25499
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spelling	oai:doaj.org-article:50b0ce6a02984f2e9ac4ed10fcb254992021-11-18T08:06:59ZEffect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.1932-620310.1371/journal.pone.0047578https://doaj.org/article/50b0ce6a02984f2e9ac4ed10fcb254992012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23226199/?tool=EBIhttps://doaj.org/toc/1932-6203In multiple sclerosis (MS), treatment with the monoclonal antibody natalizumab effectively reduces the formation of acute lesions in the central nervous system (CNS). Natalizumab binds the integrin very late antigen (VLA)-4, expressed on the surface of immune cells, and inhibits VLA-4 dependent transmigration of circulating immune-cells across the vascular endothelium into the CNS. Recent studies suggested that natalizumab treated MS patients have an increased T-cell pool in the blood compartment which may be selectively enriched in activated T-cells. Proposed causes are sequestration of activated T-cells due to reduced extravasation of activated and pro-inflammatory T-cells or due to induction of VLA-4 mediated co-stimulatory signals by natalizumab. In this study we examined how natalizumab treatment altered the distribution of effector and memory T-cell subsets in the blood compartment and if T-cells in general or myelin-reactive T-cells in particular showed signs of increased immune activation. Furthermore we examined the effects of natalizumab on CD4(+) T-cell responses to myelin in vitro. Natalizumab-treated MS patients had significantly increased numbers of effector-memory T-cells in the blood. In T-cells from natalizumab-treated MS patients, the expression of TNF-α mRNA was increased whereas the expression of fourteen other effector cytokines or transcription factors was unchanged. Natalizumab-treated MS patients had significantly decreased expression of the co-stimulatory molecule CD134 on CD4(+)CD26(HIGH) T-cells, in blood, and natalizumab decreased the expression of CD134 on MBP-reactive CD26(HIGH)CD4(+) T-cells in vitro. Otherwise CD4(+) T-cells from natalizumab-treated and untreated MS patients showed similar responses to MBP. In conclusion natalizumab treatment selectively increased the effector memory T-cell pool but not the activation state of T-cells in the blood compartment. Myelin-reactive T-cells were not selectively increased in natalizumab treated MS.Lars BörnsenJeppe Romme ChristensenRikke RatzerAnnette Bang OturaiPer Soelberg SørensenHelle Bach SøndergaardFinn SellebjergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e47578 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lars Börnsen Jeppe Romme Christensen Rikke Ratzer Annette Bang Oturai Per Soelberg Sørensen Helle Bach Søndergaard Finn Sellebjerg Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.
description	In multiple sclerosis (MS), treatment with the monoclonal antibody natalizumab effectively reduces the formation of acute lesions in the central nervous system (CNS). Natalizumab binds the integrin very late antigen (VLA)-4, expressed on the surface of immune cells, and inhibits VLA-4 dependent transmigration of circulating immune-cells across the vascular endothelium into the CNS. Recent studies suggested that natalizumab treated MS patients have an increased T-cell pool in the blood compartment which may be selectively enriched in activated T-cells. Proposed causes are sequestration of activated T-cells due to reduced extravasation of activated and pro-inflammatory T-cells or due to induction of VLA-4 mediated co-stimulatory signals by natalizumab. In this study we examined how natalizumab treatment altered the distribution of effector and memory T-cell subsets in the blood compartment and if T-cells in general or myelin-reactive T-cells in particular showed signs of increased immune activation. Furthermore we examined the effects of natalizumab on CD4(+) T-cell responses to myelin in vitro. Natalizumab-treated MS patients had significantly increased numbers of effector-memory T-cells in the blood. In T-cells from natalizumab-treated MS patients, the expression of TNF-α mRNA was increased whereas the expression of fourteen other effector cytokines or transcription factors was unchanged. Natalizumab-treated MS patients had significantly decreased expression of the co-stimulatory molecule CD134 on CD4(+)CD26(HIGH) T-cells, in blood, and natalizumab decreased the expression of CD134 on MBP-reactive CD26(HIGH)CD4(+) T-cells in vitro. Otherwise CD4(+) T-cells from natalizumab-treated and untreated MS patients showed similar responses to MBP. In conclusion natalizumab treatment selectively increased the effector memory T-cell pool but not the activation state of T-cells in the blood compartment. Myelin-reactive T-cells were not selectively increased in natalizumab treated MS.
format	article
author	Lars Börnsen Jeppe Romme Christensen Rikke Ratzer Annette Bang Oturai Per Soelberg Sørensen Helle Bach Søndergaard Finn Sellebjerg
author_facet	Lars Börnsen Jeppe Romme Christensen Rikke Ratzer Annette Bang Oturai Per Soelberg Sørensen Helle Bach Søndergaard Finn Sellebjerg
author_sort	Lars Börnsen
title	Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.
title_short	Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.
title_full	Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.
title_fullStr	Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.
title_full_unstemmed	Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.
title_sort	effect of natalizumab on circulating cd4+ t-cells in multiple sclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/50b0ce6a02984f2e9ac4ed10fcb25499
work_keys_str_mv	AT larsbornsen effectofnatalizumaboncirculatingcd4tcellsinmultiplesclerosis AT jepperommechristensen effectofnatalizumaboncirculatingcd4tcellsinmultiplesclerosis AT rikkeratzer effectofnatalizumaboncirculatingcd4tcellsinmultiplesclerosis AT annettebangoturai effectofnatalizumaboncirculatingcd4tcellsinmultiplesclerosis AT persoelbergsørensen effectofnatalizumaboncirculatingcd4tcellsinmultiplesclerosis AT hellebachsøndergaard effectofnatalizumaboncirculatingcd4tcellsinmultiplesclerosis AT finnsellebjerg effectofnatalizumaboncirculatingcd4tcellsinmultiplesclerosis
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Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis.

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