Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses

Abstract T‐cell responses to infections and cancers are regulated by co‐signalling receptors grouped into the binary categories of co‐stimulation or co‐inhibition. The co‐stimulation TNF receptor superfamily (TNFRSF) members 4‐1BB, CD27, GITR and OX40 have similar signalling mechanisms raising the q...

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Autores principales:	John Nguyen, Johannes Pettmann, Philipp Kruger, Omer Dushek
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	co‐stimulation modelling quantitative phenotypes T cells tumour necrosis factor receptor superfamily Biology (General) QH301-705.5 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b3e52d9a0e4f482f91381dbc37aef416
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spelling	oai:doaj.org-article:b3e52d9a0e4f482f91381dbc37aef4162021-11-29T08:21:36ZQuantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses1744-429210.15252/msb.202110560https://doaj.org/article/b3e52d9a0e4f482f91381dbc37aef4162021-11-01T00:00:00Zhttps://doi.org/10.15252/msb.202110560https://doaj.org/toc/1744-4292Abstract T‐cell responses to infections and cancers are regulated by co‐signalling receptors grouped into the binary categories of co‐stimulation or co‐inhibition. The co‐stimulation TNF receptor superfamily (TNFRSF) members 4‐1BB, CD27, GITR and OX40 have similar signalling mechanisms raising the question of whether they have similar impacts on T‐cell responses. Here, we screened for the quantitative impact of these TNFRSFs on primary human CD8+ T‐cell cytokine production. Although both 4‐1BB and CD27 increased production, only 4‐1BB was able to prolong the duration over which cytokine was produced, and both had only modest effects on antigen sensitivity. An operational model explained these different phenotypes using shared signalling based on the surface expression of 4‐1BB being regulated through signalling feedback. The model predicted and experiments confirmed that CD27 co‐stimulation increases 4‐1BB expression and subsequent 4‐1BB co‐stimulation. GITR and OX40 displayed only minor effects on their own but, like 4‐1BB, CD27 could enhance GITR expression and subsequent GITR co‐stimulation. Thus, different co‐stimulation receptors can have different quantitative effects allowing for synergy and fine‐tuning of T‐cell responses.John NguyenJohannes PettmannPhilipp KrugerOmer DushekWileyarticleco‐stimulationmodellingquantitative phenotypesT cellstumour necrosis factor receptor superfamilyBiology (General)QH301-705.5Medicine (General)R5-920ENMolecular Systems Biology, Vol 17, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	co‐stimulation modelling quantitative phenotypes T cells tumour necrosis factor receptor superfamily Biology (General) QH301-705.5 Medicine (General) R5-920
spellingShingle	co‐stimulation modelling quantitative phenotypes T cells tumour necrosis factor receptor superfamily Biology (General) QH301-705.5 Medicine (General) R5-920 John Nguyen Johannes Pettmann Philipp Kruger Omer Dushek Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses
description	Abstract T‐cell responses to infections and cancers are regulated by co‐signalling receptors grouped into the binary categories of co‐stimulation or co‐inhibition. The co‐stimulation TNF receptor superfamily (TNFRSF) members 4‐1BB, CD27, GITR and OX40 have similar signalling mechanisms raising the question of whether they have similar impacts on T‐cell responses. Here, we screened for the quantitative impact of these TNFRSFs on primary human CD8+ T‐cell cytokine production. Although both 4‐1BB and CD27 increased production, only 4‐1BB was able to prolong the duration over which cytokine was produced, and both had only modest effects on antigen sensitivity. An operational model explained these different phenotypes using shared signalling based on the surface expression of 4‐1BB being regulated through signalling feedback. The model predicted and experiments confirmed that CD27 co‐stimulation increases 4‐1BB expression and subsequent 4‐1BB co‐stimulation. GITR and OX40 displayed only minor effects on their own but, like 4‐1BB, CD27 could enhance GITR expression and subsequent GITR co‐stimulation. Thus, different co‐stimulation receptors can have different quantitative effects allowing for synergy and fine‐tuning of T‐cell responses.
format	article
author	John Nguyen Johannes Pettmann Philipp Kruger Omer Dushek
author_facet	John Nguyen Johannes Pettmann Philipp Kruger Omer Dushek
author_sort	John Nguyen
title	Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses
title_short	Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses
title_full	Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses
title_fullStr	Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses
title_full_unstemmed	Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses
title_sort	quantitative contributions of tnf receptor superfamily members to cd8+ t‐cell responses
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/b3e52d9a0e4f482f91381dbc37aef416
work_keys_str_mv	AT johnnguyen quantitativecontributionsoftnfreceptorsuperfamilymemberstocd8tcellresponses AT johannespettmann quantitativecontributionsoftnfreceptorsuperfamilymemberstocd8tcellresponses AT philippkruger quantitativecontributionsoftnfreceptorsuperfamilymemberstocd8tcellresponses AT omerdushek quantitativecontributionsoftnfreceptorsuperfamilymemberstocd8tcellresponses
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Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses

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