Pathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany a suboptimal CD8(+) t-cell response: reversal by adenoviral vaccine

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dc.contributor.authorVasconcelos, Jose Ronnie Carvalho de [UNIFESP]
dc.contributor.authorBruna-Romero, Oscar
dc.contributor.authorAraujo, Adriano Fernando [UNIFESP]
dc.contributor.authorDominguez, Mariana Ribeiro [UNIFESP]
dc.contributor.authorErsching, Jonatan [UNIFESP]
dc.contributor.authorAlencar, Bruna Cunha Gondim de [UNIFESP]
dc.contributor.authorMachado, Alexandre Vieira
dc.contributor.authorGazzinelli, Ricardo Tostes
dc.contributor.authorBortoluci, Karina Ramalho [UNIFESP]
dc.contributor.authorAmarante-Mendes, Gustavo Pessini
dc.contributor.authorLopes, Marcela de Freitas
dc.contributor.authorRodrigues, Mauricio Martins [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionFiocruz MS
dc.contributor.institutionUniv Massachusetts
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.date.accessioned2016-01-24T14:27:09Z
dc.date.available2016-01-24T14:27:09Z
dc.date.issued2012-05-01
dc.description.abstractMHC class la-restricted CD8(+) T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8(+) T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8(+) T-cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. for that purpose, we compared the CD8(+) T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8(+) T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8(+) cells expanded during infection. in parallel, infected adenovirus-vaccinated mice had a stronger CD8(+) T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8(+) T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination.en
dc.description.affiliationUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG, Brazil
dc.description.affiliationFiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA
dc.description.affiliationUniversidade Federal de São Paulo, Dept Ciencias Biol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 São Paulo, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio de Janeiro, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Ciencias Biol, Escola Paulista Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipMillennium Institute for Gene Therapy (Brazil)
dc.description.sponsorshipIDFAPESP: 2006/1983-4
dc.description.sponsorshipIDFAPESP: 2009/06820-4
dc.description.sponsorshipIDCNPq: 420067/2005-1
dc.format.extent16
dc.identifierhttps://dx.doi.org/10.1371/journal.ppat.1002699
dc.identifier.citationPlos Pathogens. San Francisco: Public Library Science, v. 8, n. 5, 16 p., 2012.
dc.identifier.doi10.1371/journal.ppat.1002699
dc.identifier.fileWOS000305322900033.pdf
dc.identifier.issn1553-7374
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/34826
dc.identifier.wosWOS:000305322900033
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos Pathogens
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titlePathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany a suboptimal CD8(+) t-cell response: reversal by adenoviral vaccineen
dc.typeinfo:eu-repo/semantics/article
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