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Open AccessArticle

Activation of OX40 and CD27 Costimulatory Signalling in Sheep through Recombinant Ovine Ligands

1
Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Valdeolmos, 28130 Madrid, Spain
2
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(2), 333; https://doi.org/10.3390/vaccines8020333
Received: 16 May 2020 / Revised: 8 June 2020 / Accepted: 18 June 2020 / Published: 22 June 2020
(This article belongs to the Section Cellular/Molecular Immunology)
Members of the tumour necrosis factor (TNF) superfamily OX40L and CD70 and their receptors are costimulating signalling axes critical for adequate T cell activation in humans and mice but characterisation of these molecules in other species including ruminants is lacking. Here we cloned and expressed the predicted ovine orthologues of the receptors OX40 and CD27, as well as soluble recombinant forms of their potential ovine ligands, OaOX40L and OaCD70. Using biochemical and immunofluorescence analyses, we show that both signalling axes are functional in sheep. We show that oligomeric recombinant ligand constructs are able to induce signalling through their receptors on transfected cells. Recombinant defective human adenoviruses were constructed to express the soluble forms of OaOX40L and OaCD70. Both proteins were detected in the supernatant of adenovirus-infected cells and shown to activate NF-κB signalling pathway through their cognate receptor. These adenovirus-secreted OaOX40L and OaCD70 forms could also activate ovine T cell proliferation and enhance IFN-γ production in CD4+ and CD8+ T cells. Altogether, this study provides the first characterisation of the ovine costimulatory OX40L-OX40 and CD70-CD27 signalling axes, and indicates that their activation in vivo may be useful to enhance vaccination-induced immune responses in sheep and other ruminants. View Full-Text
Keywords: T cell costimulatory signal; ovine immunology; TNF receptor; OX40; CD27 T cell costimulatory signal; ovine immunology; TNF receptor; OX40; CD27
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Rojas, J.M.; Alejo, A.; Avia, J.M.; Rodríguez-Martín, D.; Sánchez, C.; Alcamí, A.; Sevilla, N.; Martín, V. Activation of OX40 and CD27 Costimulatory Signalling in Sheep through Recombinant Ovine Ligands. Vaccines 2020, 8, 333.

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