Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion.
Identifieur interne : 002785 ( PubMed/Curation ); précédent : 002784; suivant : 002786Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion.
Auteurs : Tommaso Lorenzi [France] ; Rebecca H. Chisholm [Australie] ; Matteo Melensi [Italie] ; Alexander Lorz [France] ; Marcello Delitala [Italie]Source :
- Immunology [ 1365-2567 ] ; 2015.
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Analyse numérique assistée par ordinateur, Animaux, Antigènes (immunologie), Facteurs temps, Humains, Immunothérapie (), Lymphocytes T (anatomopathologie), Lymphocytes T (immunologie), Modèles immunologiques, Mort cellulaire, Mémoire immunologique, Prolifération cellulaire, Simulation numérique, Échappement immunitaire.
- MESH :
- anatomopathologie : Lymphocytes T.
- immunologie : Antigènes, Lymphocytes T.
- Activation des lymphocytes, Analyse numérique assistée par ordinateur, Animaux, Facteurs temps, Humains, Immunothérapie, Modèles immunologiques, Mort cellulaire, Mémoire immunologique, Prolifération cellulaire, Simulation numérique, Échappement immunitaire.
English descriptors
- KwdEn :
- Animals, Antigens (immunology), Cell Death, Cell Proliferation, Computer Simulation, Humans, Immune Evasion, Immunologic Memory, Immunotherapy (methods), Lymphocyte Activation, Models, Immunological, Numerical Analysis, Computer-Assisted, T-Lymphocytes (immunology), T-Lymphocytes (pathology), Time Factors.
- MESH :
- chemical , immunology : Antigens.
- immunology : T-Lymphocytes.
- methods : Immunotherapy.
- pathology : T-Lymphocytes.
- Animals, Cell Death, Cell Proliferation, Computer Simulation, Humans, Immune Evasion, Immunologic Memory, Lymphocyte Activation, Models, Immunological, Numerical Analysis, Computer-Assisted, Time Factors.
Abstract
T cells are key players in immune action against the invasion of target cells expressing non-self antigens. During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in 'chase-and-escape' dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.
DOI: 10.1111/imm.12500
PubMed: 26119966
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During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in 'chase-and-escape' dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26119966</PMID><DateCreated><Year>2015</Year><Month>09</Month><Day>16</Day></DateCreated><DateCompleted><Year>2015</Year><Month>12</Month><Day>17</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1365-2567</ISSN><JournalIssue CitedMedium="Internet"><Volume>146</Volume><Issue>2</Issue><PubDate><Year>2015</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Immunology</Title><ISOAbbreviation>Immunology</ISOAbbreviation></Journal><ArticleTitle>Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion.</ArticleTitle><Pagination><MedlinePgn>271-80</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/imm.12500</ELocationID><Abstract><AbstractText>T cells are key players in immune action against the invasion of target cells expressing non-self antigens. During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in 'chase-and-escape' dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.</AbstractText><CopyrightInformation>© 2015 John Wiley & Sons Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lorenzi</LastName><ForeName>Tommaso</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan Cedex, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chisholm</LastName><ForeName>Rebecca H</ForeName><Initials>RH</Initials><AffiliationInfo><Affiliation>School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Melensi</LastName><ForeName>Matteo</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Health Sciences, A. Avogadro Università del Piemonte Orientale, Novara, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lorz</LastName><ForeName>Alexander</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>MAMBA Team, INRIA-Paris-Rocquencourt, Le Chesnay Cedex, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire Jacques-Louis Lions, Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire Jacques-Louis Lions, CNRS, UMR 7598, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Delitala</LastName><ForeName>Marcello</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Mathematical Sciences, Politecnico di Torino, Torino, Italy.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>08</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Immunology</MedlineTA><NlmUniqueID>0374672</NlmUniqueID><ISSNLinking>0019-2805</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000941">Antigens</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Immunol. 2006 Dec 1;177(11):7698-706</RefSource><PMID Version="1">17114440</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Math Biosci. 2014 Jul;253:50-62</RefSource><PMID Version="1">24759513</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Blood. 2006 Sep 15;108(6):1949-56</RefSource><PMID 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MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000941" MajorTopicYN="N">Antigens</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016923" MajorTopicYN="N">Cell Death</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003198" MajorTopicYN="Y">Computer Simulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057131" MajorTopicYN="Y">Immune Evasion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007156" MajorTopicYN="N">Immunologic Memory</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007167" MajorTopicYN="N">Immunotherapy</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008213" MajorTopicYN="Y">Lymphocyte Activation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018448" MajorTopicYN="Y">Models, Immunological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009716" MajorTopicYN="N">Numerical Analysis, Computer-Assisted</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013601" MajorTopicYN="N">T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4582968 [Available on 10/01/16]</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">T cells</Keyword><Keyword MajorTopicYN="N">mathematical modelling</Keyword><Keyword MajorTopicYN="N">memory</Keyword><Keyword MajorTopicYN="N">theoretical immunology</Keyword><Keyword MajorTopicYN="N">vaccination</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>03</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>06</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>06</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>6</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>6</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>12</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId 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