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T-Cell-specific loss of the PI-3-linase p110? catalytic subunit results in enhanced cytokine production and antitumor response

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dc.creatorAragoneses-Fenoll, Lauraspa
dc.creatorOjeda, Gloriaspa
dc.creatorMontes-Casado, Maríaspa
dc.creatorAcosta Ampudia, Yeny Yasbleidyspa
dc.creatorDianzani, Umbertospa
dc.creatorPortolés, Pilarspa
dc.creatorRojo, José M.spa
dc.date.accessioned2020-08-06T16:20:23Z
dc.date.available2020-08-06T16:20:23Z
dc.date.created2018-02-27spa
dc.description.abstractClass IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110? and p110? are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110? PI3K in normal or pathological immune responses is well established, yet the importance of p110? subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110? conditionally deleted in CD4+ and CD8+ T lymphocytes (p110??/??T) were used. p110??/??T mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen. “In vitro,” TCR/CD3 plus CD28 activation of naive CD4+ and CD8+ p110??/??T T cells showed enhanced effector function, particularly IFN-? secretion, T-bet induction, and Akt, Erk, or P38 activation. Tfh derived from p110??/??T cells also have enhanced responses when compared to normal mice, and IL-2 expanded p110??/??T CD8+ T cells had enhanced levels of LAMP-1 and Granzyme B. By contrast, the expansion of p110??/??T iTreg cells was diminished. Also, p110??/??T mice had enhanced anti-keyhole limpet hemocyanin (KLH) IFN-?, or IL-4 responses and IgG1 and IgG2b anti-KLH antibodies, using CFA or Alum as adjuvant, respectively. When compared to WT mice, p110??/??T mice inoculated with B16.F10 melanoma showed delayed tumor progression. The percentage of CD8+ T lymphocytes was higher and the percentage of Treg cells lower in the spleen of tumor-bearing p110??/??T mice. Also, IFN-? production in tumor antigen-activated spleen cells was enhanced. Thus, PI3K p110? plays a significant role in antigen activation and differentiation of CD4+ and CD8+ T lymphocytes modulating antitumor immunity.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.3389/fimmu.2018.00332
dc.identifier.issnEISSN: 1664-3224
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/25984
dc.language.isoengspa
dc.publisherFrontiers Social Mediaspa
dc.relation.citationTitleFrontiers in Immunology
dc.relation.citationVolumeVol. 9
dc.relation.ispartofFrontiers in Immunology, EISSN: 1664-3224, Vol.9 (February 2018); 14 pp.spa
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2018.00332/fullspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.sourceFrontiers in Immunologyspa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subject.keywordPI3Kspa
dc.subject.keywordPI3-kinase alpha subunitspa
dc.subject.keywordT lymphocytesspa
dc.subject.keywordCD28 costimulationspa
dc.subject.keywordAnti-KLH responsespa
dc.subject.keywordMelanomaspa
dc.titleT-Cell-specific loss of the PI-3-linase p110? catalytic subunit results in enhanced cytokine production and antitumor responsespa
dc.title.TranslatedTitleLa pérdida específica de células T de la subunidad catalítica p110? de PI-3-linasa da como resultado una producción mejorada de citocinas y una respuesta antitumoralspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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