LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8(+) T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infection

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dc.citation.volume8
dc.contributor.authorFerreira, Camila Pontes [UNIFESP]
dc.contributor.authorCariste, Leonardo Moro [UNIFESP]
dc.contributor.authorVirgilio, Fernando dos Santos [UNIFESP]
dc.contributor.authorMoraschi, Barbara Ferri [UNIFESP]
dc.contributor.authorMonteiro, Caroline Brandao [UNIFESP]
dc.contributor.authorMachado, Alexandre de Magalhaes Vieira
dc.contributor.authorGazzinelli, Ricardo Tostes
dc.contributor.authorBruna-Romero, Oscar
dc.contributor.authorRuiz, Pedro Luiz Menin [UNIFESP]
dc.contributor.authorRibeiro, Daniel Araki [UNIFESP]
dc.contributor.authorLannes-Vieira, Joseli
dc.contributor.authorLopes, Marcela de Freitas
dc.contributor.authorRodrigues, Mauricio Martins [UNIFESP]
dc.contributor.authorVasconcelos, Jose Ronnie Carvalho de [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.coverageLausanne
dc.date.accessioned2020-08-04T13:39:51Z
dc.date.available2020-08-04T13:39:51Z
dc.date.issued2017
dc.description.abstractIntegrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as Trypanosoma cruzi, the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8(+) T cells generated by heterologous prime-boost immunization during experimental infection with T. cruzi. To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules. After anti-LFA-1, but not anti-VLA-4 treatment, all vaccinated mice displayed increased blood and tissue parasitemia, and quickly succumbed to infection. In addition, there was an accumulation of specific CD8(+) T cells in the spleen and lymph nodes and a decrease in the number of those cells, especially in the heart, suggesting that LFA-1 is important for the output of specific CD8(+) T cells from secondary lymphoid organs into infected organs such as the heart. The treatment did not alter CD8(+) T cell effector functions such as the production of pro-inflammatory cytokines and granzyme B, and maintained the proliferative capacity after treatment. However, the specific CD8(+) T cell direct cytotoxicity was impaired after LFA-1 blockade. Also, these cells expressed higher levels of Fas/CD95 on the surface, suggesting that they are susceptible to programmed cell death by the extrinsic pathway. We conclude that LFA-1 plays an important role in the migration of specific CD8(+) T cells and in the direct cytotoxicity of these cells.en
dc.description.affiliationCtr Mol & Cellular Therapy, Mol Immunol Lab, Sao Paulo, Brazil
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biosci, Sao Paulo, Brazil
dc.description.affiliationFiocruz MS, Rene Rachou Res Ctr, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA
dc.description.affiliationUniv Fed Santa Catarina, Dept Microbiol Immunol & Parasitol, Florianopolis, SC, Brazil
dc.description.affiliationFiocruz MS, Oswaldo Cruz Inst, Biol Interact Lab, Rio De Janeiro, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biosci, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt
dc.description.sponsorshipUS National Institutes of Health (NIAID)en
dc.description.sponsorshipIDFAPESP: 2012/22514-3pt
dc.description.sponsorshipIDFAPESP: 2015/08814-2pt
dc.description.sponsorshipIDFAPESP: 2017/11499-7pt
dc.description.sponsorshipIDFAPESP: 2014/19422-5pt
dc.description.sponsorshipIDNIAID: R01AI116577en
dc.format.extent-
dc.identifierhttps://dx.doi.org/10.3389/fimmu.2017.01291
dc.identifier.citationFrontiers In Immunology. Lausanne, v. 8, p. -, 2017.
dc.identifier.doi10.3389/fimmu.2017.01291
dc.identifier.fileWOS000412868400001.pdf
dc.identifier.issn1664-3224
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57150
dc.identifier.wosWOS:000412868400001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Immunology
dc.rightsAcesso aberto
dc.subjectVaccinationen
dc.subjectTrypanosoma cruzien
dc.subjectMigrationen
dc.subjectIntegrinsen
dc.subjectSpecific CD8(+) T cellsen
dc.titleLFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8(+) T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infectionen
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