Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness.
Identifieur interne : 000C95 ( Main/Exploration ); précédent : 000C94; suivant : 000C96Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness.
Auteurs : Virginia A. Pedicord [États-Unis] ; Justin R. Cross [États-Unis] ; Welby Montalvo-Ortiz [États-Unis] ; Martin L. Miller [États-Unis] ; James P. Allison [États-Unis]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2015.
Descripteurs français
- KwdFr :
- Activation des lymphocytes (MeSH), Animaux (MeSH), Anticorps monoclonaux (pharmacologie), Antigène CTLA-4 (antagonistes et inhibiteurs), Antigène CTLA-4 (génétique), Antigène CTLA-4 (immunologie), Différenciation cellulaire (MeSH), Infections à Listeria (anatomopathologie), Infections à Listeria (génétique), Infections à Listeria (immunologie), Infections à Listeria (microbiologie), Listeria monocytogenes (immunologie), Lymphocytes T CD8+ (anatomopathologie), Lymphocytes T CD8+ (immunologie), Lymphocytes T CD8+ (microbiologie), Lymphomes (anatomopathologie), Lymphomes (génétique), Lymphomes (immunologie), Mémoire immunologique (MeSH), Ovalbumine (génétique), Ovalbumine (immunologie), Prolifération cellulaire (MeSH), Régulation de l'expression des gènes (MeSH), Sirolimus (pharmacologie), Souris (MeSH), Souris de lignée C57BL (MeSH), Souris transgéniques (MeSH), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (immunologie), Transduction du signal (MeSH).
- MESH :
- anatomopathologie : Infections à Listeria, Lymphocytes T CD8+, Lymphomes.
- antagonistes et inhibiteurs : Antigène CTLA-4, Sérine-thréonine kinases TOR.
- génétique : Antigène CTLA-4, Infections à Listeria, Lymphomes, Ovalbumine, Sérine-thréonine kinases TOR.
- immunologie : Antigène CTLA-4, Infections à Listeria, Listeria monocytogenes, Lymphocytes T CD8+, Lymphomes, Ovalbumine, Sérine-thréonine kinases TOR.
- microbiologie : Infections à Listeria, Lymphocytes T CD8+.
- pharmacologie : Anticorps monoclonaux, Sirolimus.
- Activation des lymphocytes, Animaux, Différenciation cellulaire, Mémoire immunologique, Prolifération cellulaire, Régulation de l'expression des gènes, Souris, Souris de lignée C57BL, Souris transgéniques, Transduction du signal.
English descriptors
- KwdEn :
- Animals (MeSH), Antibodies, Monoclonal (pharmacology), CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (microbiology), CD8-Positive T-Lymphocytes (pathology), CTLA-4 Antigen (antagonists & inhibitors), CTLA-4 Antigen (genetics), CTLA-4 Antigen (immunology), Cell Differentiation (MeSH), Cell Proliferation (MeSH), Gene Expression Regulation (MeSH), Immunologic Memory (MeSH), Listeria monocytogenes (immunology), Listeriosis (genetics), Listeriosis (immunology), Listeriosis (microbiology), Listeriosis (pathology), Lymphocyte Activation (MeSH), Lymphoma (genetics), Lymphoma (immunology), Lymphoma (pathology), Mice (MeSH), Mice, Inbred C57BL (MeSH), Mice, Transgenic (MeSH), Ovalbumin (genetics), Ovalbumin (immunology), Signal Transduction (MeSH), Sirolimus (pharmacology), TOR Serine-Threonine Kinases (antagonists & inhibitors), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (immunology).
- MESH :
- chemical , antagonists & inhibitors : CTLA-4 Antigen, TOR Serine-Threonine Kinases.
- chemical , genetics : CTLA-4 Antigen, Ovalbumin, TOR Serine-Threonine Kinases.
- chemical , immunology : CTLA-4 Antigen, Ovalbumin, TOR Serine-Threonine Kinases.
- chemical , pharmacology : Antibodies, Monoclonal, Sirolimus.
- genetics : Listeriosis, Lymphoma.
- immunology : CD8-Positive T-Lymphocytes, Listeria monocytogenes, Listeriosis, Lymphoma.
- microbiology : CD8-Positive T-Lymphocytes, Listeriosis.
- pathology : CD8-Positive T-Lymphocytes, Listeriosis, Lymphoma.
- Animals, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Immunologic Memory, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Signal Transduction.
Abstract
During primary Ag encounter, T cells receive numerous positive and negative signals that control their proliferation, function, and differentiation, but how these signals are integrated to modulate T cell memory has not been fully characterized. In these studies, we demonstrate that combining seemingly opposite signals, CTLA-4 blockade and rapamycin-mediated mammalian target of rapamycin inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8(+) T cells and improved memory responses to tumors and bacterial challenges. This enhanced efficacy corresponds to increased early expansion and memory precursor differentiation of CD8(+) T cells and increased mitochondrial biogenesis and spare respiratory capacity in memory CD8(+) T cells in mice treated with anti-CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mammalian target of rapamycin inhibition cooperates with rather than antagonizes blockade of CTLA-4, promoting unrestrained effector function and proliferation, and an optimal metabolic program for CD8(+) T cell memory.
DOI: 10.4049/jimmunol.1402390
PubMed: 25624453
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Antibodies, Monoclonal (pharmacology)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>CD8-Positive T-Lymphocytes (microbiology)</term>
<term>CD8-Positive T-Lymphocytes (pathology)</term>
<term>CTLA-4 Antigen (antagonists & inhibitors)</term>
<term>CTLA-4 Antigen (genetics)</term>
<term>CTLA-4 Antigen (immunology)</term>
<term>Cell Differentiation (MeSH)</term>
<term>Cell Proliferation (MeSH)</term>
<term>Gene Expression Regulation (MeSH)</term>
<term>Immunologic Memory (MeSH)</term>
<term>Listeria monocytogenes (immunology)</term>
<term>Listeriosis (genetics)</term>
<term>Listeriosis (immunology)</term>
<term>Listeriosis (microbiology)</term>
<term>Listeriosis (pathology)</term>
<term>Lymphocyte Activation (MeSH)</term>
<term>Lymphoma (genetics)</term>
<term>Lymphoma (immunology)</term>
<term>Lymphoma (pathology)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Mice, Transgenic (MeSH)</term>
<term>Ovalbumin (genetics)</term>
<term>Ovalbumin (immunology)</term>
<term>Signal Transduction (MeSH)</term>
<term>Sirolimus (pharmacology)</term>
<term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term>
<term>TOR Serine-Threonine Kinases (genetics)</term>
<term>TOR Serine-Threonine Kinases (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Anticorps monoclonaux (pharmacologie)</term>
<term>Antigène CTLA-4 (antagonistes et inhibiteurs)</term>
<term>Antigène CTLA-4 (génétique)</term>
<term>Antigène CTLA-4 (immunologie)</term>
<term>Différenciation cellulaire (MeSH)</term>
<term>Infections à Listeria (anatomopathologie)</term>
<term>Infections à Listeria (génétique)</term>
<term>Infections à Listeria (immunologie)</term>
<term>Infections à Listeria (microbiologie)</term>
<term>Listeria monocytogenes (immunologie)</term>
<term>Lymphocytes T CD8+ (anatomopathologie)</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Lymphocytes T CD8+ (microbiologie)</term>
<term>Lymphomes (anatomopathologie)</term>
<term>Lymphomes (génétique)</term>
<term>Lymphomes (immunologie)</term>
<term>Mémoire immunologique (MeSH)</term>
<term>Ovalbumine (génétique)</term>
<term>Ovalbumine (immunologie)</term>
<term>Prolifération cellulaire (MeSH)</term>
<term>Régulation de l'expression des gènes (MeSH)</term>
<term>Sirolimus (pharmacologie)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Souris transgéniques (MeSH)</term>
<term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term>
<term>Sérine-thréonine kinases TOR (génétique)</term>
<term>Sérine-thréonine kinases TOR (immunologie)</term>
<term>Transduction du signal (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>CTLA-4 Antigen</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>CTLA-4 Antigen</term>
<term>Ovalbumin</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>CTLA-4 Antigen</term>
<term>Ovalbumin</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à Listeria</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphomes</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Antigène CTLA-4</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Listeriosis</term>
<term>Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigène CTLA-4</term>
<term>Infections à Listeria</term>
<term>Lymphomes</term>
<term>Ovalbumine</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigène CTLA-4</term>
<term>Infections à Listeria</term>
<term>Listeria monocytogenes</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphomes</term>
<term>Ovalbumine</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
<term>Listeria monocytogenes</term>
<term>Listeriosis</term>
<term>Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Infections à Listeria</term>
<term>Lymphocytes T CD8+</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
<term>Listeriosis</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
<term>Listeriosis</term>
<term>Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Anticorps monoclonaux</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Differentiation</term>
<term>Cell Proliferation</term>
<term>Gene Expression Regulation</term>
<term>Immunologic Memory</term>
<term>Lymphocyte Activation</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term>
<term>Animaux</term>
<term>Différenciation cellulaire</term>
<term>Mémoire immunologique</term>
<term>Prolifération cellulaire</term>
<term>Régulation de l'expression des gènes</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
<term>Transduction du signal</term>
</keywords>
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<front><div type="abstract" xml:lang="en">During primary Ag encounter, T cells receive numerous positive and negative signals that control their proliferation, function, and differentiation, but how these signals are integrated to modulate T cell memory has not been fully characterized. In these studies, we demonstrate that combining seemingly opposite signals, CTLA-4 blockade and rapamycin-mediated mammalian target of rapamycin inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8(+) T cells and improved memory responses to tumors and bacterial challenges. This enhanced efficacy corresponds to increased early expansion and memory precursor differentiation of CD8(+) T cells and increased mitochondrial biogenesis and spare respiratory capacity in memory CD8(+) T cells in mice treated with anti-CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mammalian target of rapamycin inhibition cooperates with rather than antagonizes blockade of CTLA-4, promoting unrestrained effector function and proliferation, and an optimal metabolic program for CD8(+) T cell memory. </div>
</front>
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<Abstract><AbstractText>During primary Ag encounter, T cells receive numerous positive and negative signals that control their proliferation, function, and differentiation, but how these signals are integrated to modulate T cell memory has not been fully characterized. In these studies, we demonstrate that combining seemingly opposite signals, CTLA-4 blockade and rapamycin-mediated mammalian target of rapamycin inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8(+) T cells and improved memory responses to tumors and bacterial challenges. This enhanced efficacy corresponds to increased early expansion and memory precursor differentiation of CD8(+) T cells and increased mitochondrial biogenesis and spare respiratory capacity in memory CD8(+) T cells in mice treated with anti-CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mammalian target of rapamycin inhibition cooperates with rather than antagonizes blockade of CTLA-4, promoting unrestrained effector function and proliferation, and an optimal metabolic program for CD8(+) T cell memory. </AbstractText>
<CopyrightInformation>Copyright © 2015 by The American Association of Immunologists, Inc.</CopyrightInformation>
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<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
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<CitationSubset>AIM</CitationSubset>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000911" MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName>
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<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
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<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName>
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<MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007156" MajorTopicYN="Y">Immunologic Memory</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008089" MajorTopicYN="N">Listeria monocytogenes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008088" MajorTopicYN="N">Listeriosis</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName>
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<MeshHeading><DescriptorName UI="D008223" MajorTopicYN="N">Lymphoma</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
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<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
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<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
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<MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName>
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<MeshHeading><DescriptorName UI="D010047" MajorTopicYN="N">Ovalbumin</DescriptorName>
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<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
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<MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
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<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
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<Day>28</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="pubmed"><Year>2015</Year>
<Month>1</Month>
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<PubMedPubDate PubStatus="medline"><Year>2015</Year>
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<Day>25</Day>
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<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">25624453</ArticleId>
<ArticleId IdType="pii">jimmunol.1402390</ArticleId>
<ArticleId IdType="doi">10.4049/jimmunol.1402390</ArticleId>
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<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>État de New York</li>
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</list>
<tree><country name="États-Unis"><region name="État de New York"><name sortKey="Pedicord, Virginia A" sort="Pedicord, Virginia A" uniqKey="Pedicord V" first="Virginia A" last="Pedicord">Virginia A. Pedicord</name>
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<name sortKey="Allison, James P" sort="Allison, James P" uniqKey="Allison J" first="James P" last="Allison">James P. Allison</name>
<name sortKey="Cross, Justin R" sort="Cross, Justin R" uniqKey="Cross J" first="Justin R" last="Cross">Justin R. Cross</name>
<name sortKey="Miller, Martin L" sort="Miller, Martin L" uniqKey="Miller M" first="Martin L" last="Miller">Martin L. Miller</name>
<name sortKey="Montalvo Ortiz, Welby" sort="Montalvo Ortiz, Welby" uniqKey="Montalvo Ortiz W" first="Welby" last="Montalvo-Ortiz">Welby Montalvo-Ortiz</name>
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