mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.
Identifieur interne : 000970 ( Main/Corpus ); précédent : 000969; suivant : 000971mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.
Auteurs : Hu Zeng ; Sivan Cohen ; Cliff Guy ; Sharad Shrestha ; Geoffrey Neale ; Scott A. Brown ; Caryn Cloer ; Rigel J. Kishton ; Xia Gao ; Ben Youngblood ; Mytrang Do ; Ming O. Li ; Jason W. Locasale ; Jeffrey C. Rathmell ; Hongbo ChiSource :
- Immunity [ 1097-4180 ] ; 2016.
English descriptors
- KwdEn :
- Animals (MeSH), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (metabolism), Cell Differentiation (immunology), Cells, Cultured (MeSH), Germinal Center (immunology), Germinal Center (metabolism), Glucose (metabolism), Immunity, Humoral (immunology), Lymphocyte Activation (immunology), Mechanistic Target of Rapamycin Complex 1 (MeSH), Mechanistic Target of Rapamycin Complex 2 (MeSH), Mice (MeSH), Mice, Inbred C57BL (MeSH), Multiprotein Complexes (immunology), Multiprotein Complexes (metabolism), Signal Transduction (immunology), T-Lymphocytes, Helper-Inducer (immunology), T-Lymphocytes, Helper-Inducer (metabolism), TOR Serine-Threonine Kinases (immunology), TOR Serine-Threonine Kinases (metabolism).
- MESH :
- chemical , immunology : Multiprotein Complexes, TOR Serine-Threonine Kinases.
- chemical , metabolism : Glucose, Multiprotein Complexes, TOR Serine-Threonine Kinases.
- immunology : CD4-Positive T-Lymphocytes, Cell Differentiation, Germinal Center, Immunity, Humoral, Lymphocyte Activation, Signal Transduction, T-Lymphocytes, Helper-Inducer.
- metabolism : CD4-Positive T-Lymphocytes, Germinal Center, T-Lymphocytes, Helper-Inducer.
- Animals, Cells, Cultured, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Mice, Mice, Inbred C57BL.
Abstract
Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.
DOI: 10.1016/j.immuni.2016.08.017
PubMed: 27637146
PubMed Central: PMC5050556
Links to Exploration step
pubmed:27637146Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.</title><author><name sortKey="Zeng, Hu" sort="Zeng, Hu" uniqKey="Zeng H" first="Hu" last="Zeng">Hu Zeng</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cohen, Sivan" sort="Cohen, Sivan" uniqKey="Cohen S" first="Sivan" last="Cohen">Sivan Cohen</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Guy, Cliff" sort="Guy, Cliff" uniqKey="Guy C" first="Cliff" last="Guy">Cliff Guy</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shrestha, Sharad" sort="Shrestha, Sharad" uniqKey="Shrestha S" first="Sharad" last="Shrestha">Sharad Shrestha</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Neale, Geoffrey" sort="Neale, Geoffrey" uniqKey="Neale G" first="Geoffrey" last="Neale">Geoffrey Neale</name><affiliation><nlm:affiliation>Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Brown, Scott A" sort="Brown, Scott A" uniqKey="Brown S" first="Scott A" last="Brown">Scott A. Brown</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cloer, Caryn" sort="Cloer, Caryn" uniqKey="Cloer C" first="Caryn" last="Cloer">Caryn Cloer</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kishton, Rigel J" sort="Kishton, Rigel J" uniqKey="Kishton R" first="Rigel J" last="Kishton">Rigel J. 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Li</name><affiliation><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Locasale, Jason W" sort="Locasale, Jason W" uniqKey="Locasale J" first="Jason W" last="Locasale">Jason W. Locasale</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rathmell, Jeffrey C" sort="Rathmell, Jeffrey C" uniqKey="Rathmell J" first="Jeffrey C" last="Rathmell">Jeffrey C. Rathmell</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Department of Pathology, Microbiology, and Immunology, and Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: jeff.rathmell@vanderbilt.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Chi, Hongbo" sort="Chi, Hongbo" uniqKey="Chi H" first="Hongbo" last="Chi">Hongbo Chi</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27637146</idno><idno type="pmid">27637146</idno><idno type="pmc">PMC5050556</idno><idno type="doi">10.1016/j.immuni.2016.08.017</idno><idno type="wicri:Area/Main/Corpus">000970</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000970</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.</title><author><name sortKey="Zeng, Hu" sort="Zeng, Hu" uniqKey="Zeng H" first="Hu" last="Zeng">Hu Zeng</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cohen, Sivan" sort="Cohen, Sivan" uniqKey="Cohen S" first="Sivan" last="Cohen">Sivan Cohen</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Guy, Cliff" sort="Guy, Cliff" uniqKey="Guy C" first="Cliff" last="Guy">Cliff Guy</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shrestha, Sharad" sort="Shrestha, Sharad" uniqKey="Shrestha S" first="Sharad" last="Shrestha">Sharad Shrestha</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Neale, Geoffrey" sort="Neale, Geoffrey" uniqKey="Neale G" first="Geoffrey" last="Neale">Geoffrey Neale</name><affiliation><nlm:affiliation>Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Brown, Scott A" sort="Brown, Scott A" uniqKey="Brown S" first="Scott A" last="Brown">Scott A. Brown</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cloer, Caryn" sort="Cloer, Caryn" uniqKey="Cloer C" first="Caryn" last="Cloer">Caryn Cloer</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kishton, Rigel J" sort="Kishton, Rigel J" uniqKey="Kishton R" first="Rigel J" last="Kishton">Rigel J. Kishton</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Gao, Xia" sort="Gao, Xia" uniqKey="Gao X" first="Xia" last="Gao">Xia Gao</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Youngblood, Ben" sort="Youngblood, Ben" uniqKey="Youngblood B" first="Ben" last="Youngblood">Ben Youngblood</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Do, Mytrang" sort="Do, Mytrang" uniqKey="Do M" first="Mytrang" last="Do">Mytrang Do</name><affiliation><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Ming O" sort="Li, Ming O" uniqKey="Li M" first="Ming O" last="Li">Ming O. Li</name><affiliation><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Locasale, Jason W" sort="Locasale, Jason W" uniqKey="Locasale J" first="Jason W" last="Locasale">Jason W. Locasale</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rathmell, Jeffrey C" sort="Rathmell, Jeffrey C" uniqKey="Rathmell J" first="Jeffrey C" last="Rathmell">Jeffrey C. Rathmell</name><affiliation><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Department of Pathology, Microbiology, and Immunology, and Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: jeff.rathmell@vanderbilt.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Chi, Hongbo" sort="Chi, Hongbo" uniqKey="Chi H" first="Hongbo" last="Chi">Hongbo Chi</name><affiliation><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Immunity</title><idno type="eISSN">1097-4180</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>CD4-Positive T-Lymphocytes (metabolism)</term><term>Cell Differentiation (immunology)</term><term>Cells, Cultured (MeSH)</term><term>Germinal Center (immunology)</term><term>Germinal Center (metabolism)</term><term>Glucose (metabolism)</term><term>Immunity, Humoral (immunology)</term><term>Lymphocyte Activation (immunology)</term><term>Mechanistic Target of Rapamycin Complex 1 (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 2 (MeSH)</term><term>Mice (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>Multiprotein Complexes (immunology)</term><term>Multiprotein Complexes (metabolism)</term><term>Signal Transduction (immunology)</term><term>T-Lymphocytes, Helper-Inducer (immunology)</term><term>T-Lymphocytes, Helper-Inducer (metabolism)</term><term>TOR Serine-Threonine Kinases (immunology)</term><term>TOR Serine-Threonine Kinases (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Multiprotein Complexes</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucose</term><term>Multiprotein Complexes</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Cell Differentiation</term><term>Germinal Center</term><term>Immunity, Humoral</term><term>Lymphocyte Activation</term><term>Signal Transduction</term><term>T-Lymphocytes, Helper-Inducer</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Germinal Center</term><term>T-Lymphocytes, Helper-Inducer</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Mechanistic Target of Rapamycin Complex 1</term><term>Mechanistic Target of Rapamycin Complex 2</term><term>Mice</term><term>Mice, Inbred C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27637146</PMID><DateCompleted><Year>2017</Year><Month>09</Month><Day>05</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1097-4180</ISSN><JournalIssue CitedMedium="Internet"><Volume>45</Volume><Issue>3</Issue><PubDate><Year>2016</Year><Month>09</Month><Day>20</Day></PubDate></JournalIssue><Title>Immunity</Title><ISOAbbreviation>Immunity</ISOAbbreviation></Journal><ArticleTitle>mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.</ArticleTitle><Pagination><MedlinePgn>540-554</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1074-7613(16)30341-7</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.immuni.2016.08.017</ELocationID><Abstract><AbstractText>Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.</AbstractText><CopyrightInformation>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zeng</LastName><ForeName>Hu</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cohen</LastName><ForeName>Sivan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guy</LastName><ForeName>Cliff</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shrestha</LastName><ForeName>Sharad</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Neale</LastName><ForeName>Geoffrey</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brown</LastName><ForeName>Scott A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cloer</LastName><ForeName>Caryn</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kishton</LastName><ForeName>Rigel J</ForeName><Initials>RJ</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Xia</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Youngblood</LastName><ForeName>Ben</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Do</LastName><ForeName>Mytrang</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ming O</ForeName><Initials>MO</Initials><AffiliationInfo><Affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Locasale</LastName><ForeName>Jason W</ForeName><Initials>JW</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rathmell</LastName><ForeName>Jeffrey C</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Department of Pathology, Microbiology, and Immunology, and Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: jeff.rathmell@vanderbilt.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chi</LastName><ForeName>Hongbo</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 CA193256</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>F31 CA183529</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 DK105550</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA008748</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R00 CA168997</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS064599</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI105887</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 CA176624</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI101407</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>09</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Immunity</MedlineTA><NlmUniqueID>9432918</NlmUniqueID><ISSNLinking>1074-7613</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D046912">Multiprotein Complexes</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076225">Mechanistic Target of Rapamycin Complex 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>IY9XDZ35W2</RegistryNumber><NameOfSubstance UI="D005947">Glucose</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" 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