Recall T cell responses to bluetongue virus produce a narrowing of the T cell repertoire

Rojas, José M.; Rodríguez-Calvo, Teresa; Sevilla, Noemı́

doi:10.1186/s13567-017-0444-3

Cited by 22 publications

(40 citation statements)

References 58 publications

(75 reference statements)

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“…In a study with bluetongue virus (BTV), virus-specific CD8 ϩ , but not CD4 ϩ , T cells expanded during the recall responses to BTV challenge. In addition, primary responses elicited a wider range of repertoire for MHC-I and MHC-II epitopes than the memory response, where a narrowed repertoire was induced in a dominant motif in VP7 (amino acid position 139 to 291) (430).…”

Section: Common Phenomena Observed In the Setting Of Heterologous Infmentioning

confidence: 99%

Virological and Immunological Outcomes of Coinfections

et al. 2018

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SUMMARYCoinfections involving viruses are being recognized to influence the disease pattern that occurs relative to that with single infection. Classically, we usually think of a clinical syndrome as the consequence of infection by a single virus that is isolated from clinical specimens. However, this biased laboratory approach omits detection of additional agents that could be contributing to the clinical outcome, including novel agents not usually considered pathogens. The presence of an additional agent may also interfere with the targeted isolation of a known virus. Viral interference, a phenomenon where one virus competitively suppresses replication of other coinfecting viruses, is the most common outcome of viral coinfections. In addition, coinfections can modulate virus virulence and cell death, thereby altering disease severity and epidemiology. Immunity to primary virus infection can also modulate immune responses to subsequent secondary infections. In this review, various virological mechanisms that determine viral persistence/exclusion during coinfections are discussed, and insights into the isolation/detection of multiple viruses are provided. We also discuss features of heterologous infections that impact the pattern of immune responsiveness that develops.

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Section: Common Phenomena Observed In the Setting Of Heterologous Infmentioning

confidence: 99%

Virological and Immunological Outcomes of Coinfections

et al. 2018

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“…Percentage of IFN-γ + cells within the CD4 + or CD8 + T cell compartment were measured. Isotype and fluorescence minus one-channel controls were used for gating strategy [37].…”

Section: Intracellular Cytokine Staining and Flow Cytometrymentioning

confidence: 99%

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

et al. 2020

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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.

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“…These differences observed between BTV2/KM/2003 and BTV12/PT/2003 ( Figure 8 ) were also found in [ 4 ], wherein BTV1 stimulated a significant IL-1β expression, but BTV8 did not. It is speculated that the abolition of IL-1β activation might be key for BTV survival in infected animals [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

The Tip Region on VP2 Protein of Bluetongue Virus Contains Potential IL-4-Inducing Amino Acid Peptide Segments

et al. 2020

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Bluetongue is an infectious viral hemorrhagic disease of domestic and wild ruminants that has a considerable economic impact on domestic ruminants. There are currently at least 29 serotypes of bluetongue virus (BTV) in the world. Noteworthily, the pathogenesis among BTV serotypes is different, even in the same animal species. In this study, BTV2/KM/2003 and BTV12/PT/2003 were used to investigate the differential immunological effects on bovine peripheral blood mononuclear cells (PBMCs). The BTV viral load and the expression of cytokine messenger RNA (mRNA) in PBMCs were measured by fluorescence-based real-time reverse-transcription PCR (qRT-PCR). The immunofluorescence assay (IFA) was applied to detect BTV signals in monocyte-derived macrophages (MDMs). The SWISS-MODEL and IL-4pred prediction tools were used to predict the interleukin 4 (IL-4)-inducing peptides in BTV-coat protein VP2. Synthetic peptides of VP2 were used to stimulate PBMCs for IL-4-inducing capability. This study demonstrated that the cytokine profiles of BTV-induced PBMCs were significantly different between BTV2/KM/2003 and BTV12/PT/2003. BTV2 preferentially activated the T helper 2 (Th2) pathway, represented by the early induction of IL-4, and likely fed back to inhibit the innate immunity. In contrast, BTV12 preferentially activated the innate immunity, represented by the induction of tumor necrosis factor -α (TNF-α) and interleukin 1 (IL-1), with only minimal subsequent IL-4. The BTV nonstructural protein 3 antibody (anti-BTV-NS3) fluorescent signals demonstrated that monocytes in PBMCs and MDMs were the preferred targets of BTV replication. Bioinformatics analysis revealed that the capability to induce IL-4 was attributed to the tip region of the VP2 protein, wherein a higher number of predicted peptide segments on BTVs were positively correlated with the allergic reaction reported in cattle. Synthetic peptides of BTV2-VP2 induced significant IL-4 within 12–24 h post-infection (hpi) in PBMCs, whereas those of BTV12 did not, consistent with the bioinformatics prediction. Bovine PBMCs and synthetic peptides together seem to serve as a good model for pursuing the BTV-induced IL-4 activity that precedes the development of an allergic reaction, although further optimization of the protocol is warranted.

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Recall T cell responses to bluetongue virus produce a narrowing of the T cell repertoire

Cited by 22 publications

References 58 publications

Virological and Immunological Outcomes of Coinfections

Virological and Immunological Outcomes of Coinfections

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

The Tip Region on VP2 Protein of Bluetongue Virus Contains Potential IL-4-Inducing Amino Acid Peptide Segments

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