Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion
Identifieur interne : 002B57 ( Main/Exploration ); précédent : 002B56; suivant : 002B58Mathematical 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 [ 0019-2805 ] ; 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.
Url:
DOI: 10.1111/imm.12500
PubMed: 26119966
PubMed Central: 4582968
Affiliations:
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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.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Italie</li></country></list><tree><country name="France"><noRegion><name sortKey="Lorenzi, Tommaso" sort="Lorenzi, Tommaso" uniqKey="Lorenzi T" first="Tommaso" last="Lorenzi">Tommaso Lorenzi</name></noRegion><name sortKey="Lorz, Alexander" sort="Lorz, Alexander" uniqKey="Lorz A" first="Alexander" last="Lorz">Alexander Lorz</name><name sortKey="Lorz, Alexander" sort="Lorz, Alexander" uniqKey="Lorz A" first="Alexander" last="Lorz">Alexander Lorz</name><name sortKey="Lorz, Alexander" sort="Lorz, Alexander" uniqKey="Lorz A" first="Alexander" last="Lorz">Alexander Lorz</name></country><country name="Australie"><noRegion><name sortKey="Chisholm, Rebecca H" sort="Chisholm, Rebecca H" uniqKey="Chisholm R" first="Rebecca H" last="Chisholm">Rebecca H. Chisholm</name></noRegion></country><country name="Italie"><noRegion><name sortKey="Melensi, Matteo" sort="Melensi, Matteo" uniqKey="Melensi M" first="Matteo" last="Melensi">Matteo Melensi</name></noRegion><name sortKey="Delitala, Marcello" sort="Delitala, Marcello" uniqKey="Delitala M" first="Marcello" last="Delitala">Marcello Delitala</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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