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The fate of CD4+ T cells under tolerance‐inducing stimulation: a modeling perspective

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dc.contributor.authorCaridade, Marta
dc.contributor.authorOliveira, Vanessa
dc.contributor.authorAgua-Doce, Ana
dc.contributor.authorGraca, Luis
dc.contributor.authorRibeiro, Ruy
dc.date.accessioned2021-12-21T16:32:45Z
dc.date.available2021-12-21T16:32:45Z
dc.date.issued2013
dc.description© 2013 Australasian Society for Immunology Inc.pt_PT
dc.description.abstractNon-depleting anti-CD4 monoclonal antibodies (MAbs) induce long-term dominant tolerance mediated by regulatory T cells in several animal models of transplantation, allergy and autoimmunity. However, despite many studies on tolerance induction following CD4 blockade, the consequences of this intervention on T-cell kinetics are still unknown. Mathematical models have been useful to understand lymphocyte dynamics, estimating rates of proliferation and cell death following an intervention. Using the same strategy, we found that CD4(+) T cells activated in vitro in the presence of non-depleting anti-CD4 MAbs are prevented from undergoing optimal proliferation and show a higher frequency of apoptosis. Although the changes are small, during the course of a proliferative response, they lead to very distinct final levels of cell numbers. The importance of these mechanisms, predicted by the mathematical model, was validated by showing that lck-driven Bcl-x(L) transgenic mice, bearing T cells resistant to apoptosis, fail to become tolerant to skin grafts following CD4-blockade. Our data show that, in addition to induction of regulatory T cells, CD4 blockade has a marked effect in the effector T-cell pool by the combined action of hindering proliferation while favoring apoptosis. It is, therefore, the combination of all those mechanisms that leads to stable tolerance.pt_PT
dc.description.abstract; ; ; ;pt_PT
dc.description.sponsorshipThis work was funded by grants number PIC/IC/82895/2007 and PTDC/SAU-TOX/114424/2009 from Fundação para a Ciência e Tecnologia, Portugal (to Luis Graca). Ruy M Ribeiro has received funding from the European Union 7th Framework Program under grant n1 PCOFUND-GA-2009-246542 and from Fundação para a Ciência e Tecnologia, Portugalpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationImmunol Cell Biol. 2013 Nov-Dec;91(10):652-660pt_PT
dc.identifier.doi10.1038/icb.2013.63pt_PT
dc.identifier.eissn1440-1711
dc.identifier.issn0818-9641
dc.identifier.urihttp://hdl.handle.net/10451/50504
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationInvariant Natural Killer T Cells in Allergic Asthma and Tolerogenic Therapy.
dc.relationWORK PLAN FOR RESEARCH FELLOWSHIP PCOFUND-GA-2009-246542
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/14401711pt_PT
dc.subjectAnti-CD4pt_PT
dc.subjectFoxp3pt_PT
dc.subjectImmune tolerancept_PT
dc.subjectMathematical modelingpt_PT
dc.subjectProliferation kineticspt_PT
dc.titleThe fate of CD4+ T cells under tolerance‐inducing stimulation: a modeling perspectivept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPIC/IC/82895/2007
oaire.awardNumberPTDC/SAU-TOX/114424/2009
oaire.awardNumberSFRH/BI/52182/2013
oaire.awardTitleInvariant Natural Killer T Cells in Allergic Asthma and Tolerogenic Therapy.
oaire.awardTitleWORK PLAN FOR RESEARCH FELLOWSHIP PCOFUND-GA-2009-246542
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F82895%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-TOX%2F114424%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBI%2F52182%2F2013/PT
oaire.citation.endPage660pt_PT
oaire.citation.issue10pt_PT
oaire.citation.startPage652pt_PT
oaire.citation.titleImmunology & Cell Biologypt_PT
oaire.citation.volume91pt_PT
oaire.fundingStream5646-ICCMS
oaire.fundingStream3599-PPCDT
person.familyNameCaridade
person.familyNameOliveira
person.familyNameAgua-Doce
person.familyNameSilva Graca
person.familyNameRibeiro
person.givenNameMarta
person.givenNameVanessa Alexandra Gonçalves de
person.givenNameAna
person.givenNameLuis Ricardo
person.givenNameRuy Miguel
person.identifierB-8887-2008
person.identifier.ciencia-id2219-6C04-8A3E
person.identifier.ciencia-id6C19-B162-F561
person.identifier.ciencia-id9A15-E40B-738F
person.identifier.orcid0000-0001-5294-1329
person.identifier.orcid0000-0001-6884-2675
person.identifier.orcid0000-0002-0466-7297
person.identifier.orcid0000-0001-6935-8500
person.identifier.orcid0000-0002-3988-8241
person.identifier.ridL-5045-2013
person.identifier.ridL-2997-2014
person.identifier.scopus-author-id15077924000
person.identifier.scopus-author-id36138488700
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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