Cargando…

A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells

Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situactivation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary hu...

Descripción completa

Detalles Bibliográficos
Autores principales: Abu-Shah, Enas, Demetriou, Philippos, Bálint, Štefan, Mayya, Viveka, Kutuzov, Mikhail A, Dushek, Omer, Dustin, Michael L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910819/
https://www.ncbi.nlm.nih.gov/pubmed/31552826
http://dx.doi.org/10.7554/eLife.48221
_version_ 1783479165343760384
author Abu-Shah, Enas
Demetriou, Philippos
Bálint, Štefan
Mayya, Viveka
Kutuzov, Mikhail A
Dushek, Omer
Dustin, Michael L
author_facet Abu-Shah, Enas
Demetriou, Philippos
Bálint, Štefan
Mayya, Viveka
Kutuzov, Mikhail A
Dushek, Omer
Dustin, Michael L
author_sort Abu-Shah, Enas
collection PubMed
description Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situactivation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary human immune cell. Our approach facilitates real-time single-cell manipulations, tracking of interactions and functional responses complemented by population-based measurements of cytokines, activation status and proliferation. As a proof of concept, we recapitulate immunological phenomenon such as CD4 T-cells' help to CD8 T-cells through enhanced maturation of DCs and the effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity.
format Online
Article
Text
id pubmed-6910819
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-69108192019-12-16 A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells Abu-Shah, Enas Demetriou, Philippos Bálint, Štefan Mayya, Viveka Kutuzov, Mikhail A Dushek, Omer Dustin, Michael L eLife Human Biology and Medicine Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situactivation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary human immune cell. Our approach facilitates real-time single-cell manipulations, tracking of interactions and functional responses complemented by population-based measurements of cytokines, activation status and proliferation. As a proof of concept, we recapitulate immunological phenomenon such as CD4 T-cells' help to CD8 T-cells through enhanced maturation of DCs and the effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity. eLife Sciences Publications, Ltd 2019-09-25 /pmc/articles/PMC6910819/ /pubmed/31552826 http://dx.doi.org/10.7554/eLife.48221 Text en © 2019, Abu-Shah et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Human Biology and Medicine
Abu-Shah, Enas
Demetriou, Philippos
Bálint, Štefan
Mayya, Viveka
Kutuzov, Mikhail A
Dushek, Omer
Dustin, Michael L
A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells
title A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells
title_full A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells
title_fullStr A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells
title_full_unstemmed A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells
title_short A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells
title_sort tissue-like platform for studying engineered quiescent human t-cells’ interactions with dendritic cells
topic Human Biology and Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910819/
https://www.ncbi.nlm.nih.gov/pubmed/31552826
http://dx.doi.org/10.7554/eLife.48221
work_keys_str_mv AT abushahenas atissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT demetriouphilippos atissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT balintstefan atissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT mayyaviveka atissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT kutuzovmikhaila atissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT dushekomer atissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT dustinmichaell atissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT abushahenas tissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT demetriouphilippos tissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT balintstefan tissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT mayyaviveka tissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT kutuzovmikhaila tissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT dushekomer tissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells
AT dustinmichaell tissuelikeplatformforstudyingengineeredquiescenthumantcellsinteractionswithdendriticcells