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dc.rights.licenceAttribution-NonCommercial 4.0 International*
dc.contributor.authorPontificia Universidad Javeriana. Facultad de Medicina. Departamento de Epidemiología Clínica y Bioestadística
dc.contributor.authorRey, L.M.
dc.contributor.authorGil, J.Á.
dc.contributor.authorRodríguez, L.S.
dc.contributor.authorÁngel, J
dc.contributor.authorFranco, M.A.
dc.contributor.authorMateus, J
dc.contributor.authorRondón, M.A.
dc.identifier.issn0022-538X / 1098-5514 (Electronic)spa
dc.sourceJournal of virology; Vol. 93 Núm. 19 (2019)spa
dc.titleLAP+ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Modelspa
dc.title.englishLAP+ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Modelspa
dc.description.tipoarticuloArtículo originalspa
dc.format.soportePapel / Electrónicospa
dc.subject.keywordNeonatal micespa
dc.subject.keywordTransforming growth factorspa
dc.subject.keywordAtencyassociated peptidespa
dc.description.abstractenglishTransforming growth factor (TGF-) has been shown to play a role in immunity against different pathogens in vitro and against parasites in vivo. However, its role in viral infections in vivo is incompletely understood. Using a neonatal mouse model of heterologous rhesus rotavirus (RV) vaccination, we show that the vaccine induced rotavirus-specific CD4 T cells, the majority of which lacked expression of KLRG1 or CD127, and a few regulatory rotavirus-specific CD4 T cells that expressed surface latency-associated peptide (LAP)–TGF-. In these mice, inhibiting TGF-, with both a neutralizing antibody and an inhibitor of TGF- receptor signaling (activin receptor-like kinase 5 inhibitor [ALK5i]), did not change the development or intensity of the mild diarrhea induced by the vaccine, the rotavirus-specific T cell response, or protection against a subsequent challenge with a murine EC-rotavirus. However, mice treated with anti-LAP antibodies had improved protection after a homologous EC-rotavirus challenge, compared with control rhesus rotavirus-immunized mice. Thus, oral vaccination with a heterologous rotavirus stimulates regulatory RVspecific CD4 LAP-positive (LAP) T cells, and depletion of LAP cells increases vaccineinduced protection. IMPORTANCE Despite the introduction of several live attenuated animal and human rotaviruses as efficient oral vaccines, rotaviruses continue to be the leading etiological agent for diarrhea mortality among children under 5 years of age worldwide. Improvement of these vaccines has been partially delayed because immunity to rotaviruses is incompletely understood. In the intestine (where rotavirus replicates), regulatory T cells that express latency-associated peptide (LAP) play a prominent role, which has been explored for many diseases but not specifically for infectious agents. In this paper, we show that neonatal mice given a live oral rotavirus vaccine develop rotavirus-specific LAP T cells and that depletion of these cells improves the efficiency of the vaccine. These findings may prove useful for the design of strategies to improve rotavirus
dc.type.localArtículo de revistaspa

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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial 4.0 International