The Brain Microvascular Endothelium Supports T Cell Proliferation and Has Potential for Alloantigen Presentation
Identifieur interne : 002909 ( Pmc/Curation ); précédent : 002908; suivant : 002910The Brain Microvascular Endothelium Supports T Cell Proliferation and Has Potential for Alloantigen Presentation
Auteurs : Julie Wheway [Australie] ; Stephanie Obeid [Australie] ; Pierre-Olivier Couraud [France] ; Valery Combes [Australie] ; Georges E. R. Grau [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4+ and CD8+ T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases.
Url:
DOI: 10.1371/journal.pone.0052586
PubMed: 23320074
PubMed Central: 3540051
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<front><div type="abstract" xml:lang="en"><p>Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4<sup>+</sup>
and CD8<sup>+</sup>
T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases.</p>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23320074</article-id>
<article-id pub-id-type="pmc">3540051</article-id>
<article-id pub-id-type="publisher-id">PONE-D-12-26463</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0052586</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Biology</subject>
<subj-group><subject>Anatomy and Physiology</subject>
<subj-group><subject>Immune Physiology</subject>
<subj-group><subject>Immune Cells</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Cells</subject>
<subj-group><subject>T Cells</subject>
</subj-group>
</subj-group>
<subj-group><subject>Immunity</subject>
<subj-group><subject>Immune Activation</subject>
</subj-group>
</subj-group>
<subj-group><subject>Immune Response</subject>
</subj-group>
</subj-group>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Immunity</subject>
<subj-group><subject>Immune Activation</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group><subject>Molecular Cell Biology</subject>
<subj-group><subject>Cellular Types</subject>
<subj-group><subject>Endothelial Cells</subject>
<subject>Immune Cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject>
<subj-group><subject>Anatomy and Physiology</subject>
<subj-group><subject>Immune Physiology</subject>
<subj-group><subject>Immune Cells</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group><subject>Clinical Immunology</subject>
<subj-group><subject>Immunity</subject>
<subj-group><subject>Immune Activation</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>The Brain Microvascular Endothelium Supports T Cell Proliferation and Has Potential for Alloantigen Presentation</article-title>
<alt-title alt-title-type="running-head">Brain Endothelium and T Cell Proliferation</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Wheway</surname>
<given-names>Julie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Obeid</surname>
<given-names>Stephanie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Couraud</surname>
<given-names>Pierre-Olivier</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Combes</surname>
<given-names>Valery</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Grau</surname>
<given-names>Georges E. R.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Unité 1016, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Unité Mixte de Recherche 8104, Centre National de la Recherche Scientifique, Paris, France</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>Université Paris Descartes, Paris, France</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Bourgeois</surname>
<given-names>Christine</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>INSERM, France</addr-line>
</aff>
<author-notes><corresp id="cor1">* E-mail: <email>julie.wheway@sydney.edu.au</email>
</corresp>
<fn fn-type="conflict"><p><bold>Competing Interests: </bold>
Co-author Dr Valery Combes is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.</p>
</fn>
<fn fn-type="con"><p>Conceived and designed the experiments: JW VC GG. Performed the experiments: JW SO. Analyzed the data: JW SO. Contributed reagents/materials/analysis tools: PC. Wrote the paper: JW VC GG.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>8</day>
<month>1</month>
<year>2013</year>
</pub-date>
<volume>8</volume>
<issue>1</issue>
<elocation-id>e52586</elocation-id>
<history><date date-type="received"><day>3</day>
<month>9</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>19</day>
<month>11</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-year>2013</copyright-year>
<copyright-holder>Wheway et al</copyright-holder>
<license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<abstract><p>Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4<sup>+</sup>
and CD8<sup>+</sup>
T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases.</p>
</abstract>
<funding-group><funding-statement>The study was funded by the National Health and Medical Research Council of Australia (<ext-link ext-link-type="uri" xlink:href="http://www.nhmrc.gov.au/">http://www.nhmrc.gov.au/</ext-link>
) project grants 1009914 and 571014 to VC and GEG; 1028241 to JW, VC and GEG; and 1022368 to GEG; fellowship 571397 to JW. Support was also provided through Rebecca L. Cooper Foundation equipment grants (<ext-link ext-link-type="uri" xlink:href="http://www.cooperfoundation.org.au/">http://www.cooperfoundation.org.au/</ext-link>
). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><page-count count="8"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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