CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection

The co-stimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming, we generated a strain of mice where CD28 i...

Full description

Bibliographic Details
Main Authors: Michelle A Linterman, Alice E Denton, Devina P Divekar, Ilona Zvetkova, Leanne Kane, Cristina Ferreira, Marc Veldhoen, Simon Clare, Gordon Dougan, Marion Espéli, Kenneth GC Smith
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2014-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/03180
id doaj-3e6354d1e25049648fe723c0c68f3d2a
record_format Article
spelling doaj-3e6354d1e25049648fe723c0c68f3d2a2021-05-04T23:30:11ZengeLife Sciences Publications LtdeLife2050-084X2014-10-01310.7554/eLife.03180CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infectionMichelle A Linterman0Alice E Denton1Devina P Divekar2Ilona Zvetkova3Leanne Kane4Cristina Ferreira5Marc Veldhoen6https://orcid.org/0000-0002-1478-9562Simon Clare7Gordon Dougan8Marion Espéli9Kenneth GC Smith10Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United KingdomDepartment of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United KingdomUniversity of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United KingdomWellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, United KingdomBabraham Research Campus, Babraham Institute, Cambridge, United KingdomBabraham Research Campus, Babraham Institute, Cambridge, United KingdomWellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, United KingdomWellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, United KingdomCambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United KingdomCambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United KingdomThe co-stimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming, we generated a strain of mice where CD28 is removed from CD4+ T cells after priming. We show that continued CD28 expression is important for effector CD4+ T cells following infection; maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. Persistent CD28 is also required for clearance of the bacterium Citrobacter rodentium from the gastrointestinal tract. Together, this study demonstrates that CD28 persistence is required for helper T cell polarization in response to infection, describing a novel function for CD28 that is distinct from its role in T cell priming.https://elifesciences.org/articles/03180CD28helper T cellinfection
collection DOAJ
language English
format Article
sources DOAJ
author Michelle A Linterman
Alice E Denton
Devina P Divekar
Ilona Zvetkova
Leanne Kane
Cristina Ferreira
Marc Veldhoen
Simon Clare
Gordon Dougan
Marion Espéli
Kenneth GC Smith
spellingShingle Michelle A Linterman
Alice E Denton
Devina P Divekar
Ilona Zvetkova
Leanne Kane
Cristina Ferreira
Marc Veldhoen
Simon Clare
Gordon Dougan
Marion Espéli
Kenneth GC Smith
CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection
eLife
CD28
helper T cell
infection
author_facet Michelle A Linterman
Alice E Denton
Devina P Divekar
Ilona Zvetkova
Leanne Kane
Cristina Ferreira
Marc Veldhoen
Simon Clare
Gordon Dougan
Marion Espéli
Kenneth GC Smith
author_sort Michelle A Linterman
title CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection
title_short CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection
title_full CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection
title_fullStr CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection
title_full_unstemmed CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection
title_sort cd28 expression is required after t cell priming for helper t cell responses and protective immunity to infection
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2014-10-01
description The co-stimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming, we generated a strain of mice where CD28 is removed from CD4+ T cells after priming. We show that continued CD28 expression is important for effector CD4+ T cells following infection; maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. Persistent CD28 is also required for clearance of the bacterium Citrobacter rodentium from the gastrointestinal tract. Together, this study demonstrates that CD28 persistence is required for helper T cell polarization in response to infection, describing a novel function for CD28 that is distinct from its role in T cell priming.
topic CD28
helper T cell
infection
url https://elifesciences.org/articles/03180
work_keys_str_mv AT michellealinterman cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT aliceedenton cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT devinapdivekar cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT ilonazvetkova cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT leannekane cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT cristinaferreira cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT marcveldhoen cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT simonclare cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT gordondougan cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT marionespeli cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
AT kennethgcsmith cd28expressionisrequiredaftertcellprimingforhelpertcellresponsesandprotectiveimmunitytoinfection
_version_ 1721476956719939584