Papel del TGF-β en la inmunidad contra los rotavirus

Franco-Cortés, Manuel Antonio

doi:10.18257/raccefyn.300

Cited by 1 publication

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“…In addition, the fact that we detected RV-T cells producing only IFN-␥, but not IL-2 or TNF-␣ (data not shown), is in agreement with our studies in children, where most RV-T cells secrete only IFN-␥, and higher frequencies seem to be detectable using the tetramers than by the intracellular cytokine assay (20,36). These findings support the hypothesis that in neonatal mice and children, RV may have developed mechanisms to evade the T cell immune response (2).…”

Section: Discussionsupporting

confidence: 91%

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

Rey

Gil

Mateus

et al. 2019

J Virol

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Transforming growth factor β (TGF-β) 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-β. In these mice, inhibiting TGF-β, with both a neutralizing antibody and an inhibitor of TGF-β 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 RV-specific CD4 LAP-positive (LAP+) T cells, and depletion of LAP+ cells increases vaccine-induced 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 vaccines.

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Section: Discussionsupporting

confidence: 91%

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

Rey

Gil

Mateus

et al. 2019

J Virol

Self Cite

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Papel del TGF-β en la inmunidad contra los rotavirus

Cited by 1 publication

References 64 publications

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

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Papel del TGF-β en la inmunidad contra los rotavirus

Cited by 1 publication

References 64 publications

LAP + Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

LAP + Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

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LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model