Dendritic cells presenting equine herpesvirus-1 antigens induce protective anti-viral immunity.

Steinbach, Falko; Borchers, Kerstin; Ricciardi‐Castagnoli, Paola; Ludwig, Hanns; Stingl, Georg; Elbe‐Bürger, Adelheid

doi:10.1099/0022-1317-79-12-3005

Cited by 16 publications

(7 citation statements)

References 59 publications

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“…An additional explanation is that the efficiency with which dendritic cells are transfected in vitro is typically low: approximately 10 %. Despite this low transfection efficiency, this report and others have shown the potential of in vitro transfection of dendritic cells for stimulating immune responses (Manickan et al, 1997;Rouse et al, 1994;Siedek et al, 1999;Steinbach et al, 1998). In the horse, we have previously demonstrated that dendritic cells outperform other autologous cells as antigen-presenting cells for the detection of memory lymphoproliferative responses (Soboll et al, 2003).…”

Section: Discussionmentioning

confidence: 74%

Identification of equine herpesvirus-1 antigens recognized by cytotoxic T lymphocytes

Soboll

Whalley

Koen

et al. 2003

Journal of General Virology

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Equine herpesvirus-1 (EHV-1) causes serious disease in horses throughout the world, despite the frequent use of vaccines. CTLs are thought to be critical for protection from primary and reactivating latent EHV-1 infections. However, the antigen-specificity of EHV-1-specific CTLs is unknown. The aim of this study was to identify EHV-1 genes that encode proteins containing CTL epitopes and to determine their MHC I (or ELA-A in the horse) restriction. Equine dendritic cells, transfected with a series of EHV-1 genes, were used to stimulate autologous CTL precursor populations derived from previously infected horses. Cytotoxicity was subsequently measured against EHV-1-infected PWM lymphoblast targets. Dendritic cells were infected with EHV-1 (positive control) or transfected with plasmids encoding the gB, gC, gD, gE, gH, gI, gL, immediateearly (IE) or early protein of EHV-1 using the PowderJect XR-1 research device. Dendritic cells transfected with the IE gene induced CTL responses in four of six ponies. All four of these ponies shared a common ELA-A3.1 haplotype. Dendritic cells transfected with gC, gD, gI and gL glycoproteins induced CTLs in individual ponies. The cytotoxic activity was ELA-A-restricted, as heterologous targets from ELA-A mismatched ponies were not killed and an MHC I blocking antibody reduced EHV-1-specific killing. This is the first identification of an EHV-1 protein containing ELA-A-restricted CTL epitopes. This assay can now be used to study CTL specificity for EHV-1 proteins in horses with a broad range of ELA-A haplotypes, with the goal of developing a multi-epitope EHV-1 vaccine.

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Section: Discussionmentioning

confidence: 74%

Identification of equine herpesvirus-1 antigens recognized by cytotoxic T lymphocytes

Soboll

Whalley

Koen

et al. 2003

Journal of General Virology

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“…In addition, there is evidence indicating that local tissue DCs are able to re-enter the bloodstream, which might facilitate the spread of pathogens from tissue to tissue, carried by DCs serving as Trojan horses (Randolph et al, 2008). Finally, DCs have been shown to play an important role during the pathogenesis of alphaherpesviruses in general (Bosnjak et al, 2005;Novak and Peng, 2005;Pollara et al, 2005), and for EHV1 in specific, both murine and equine blood-derived DCs are susceptible to EHV1 in vitro (Siedek et al, 1999;Steinbach et al, 1998). Unfortunately, little is known about equine DCs in A c c e p t e d M a n u s c r i p t 21 general and mucosal DCs in specific in this species, and more research is needed to elucidate the role of DCs in EHV1 infection and/or other viral infections in equines.…”

Section: Discussionmentioning

confidence: 99%

Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses

Gryspeerdt

Vandekerckhove

Garré

et al. 2010

Veterinary Microbiology

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Equine herpesvirus 1 (EHV1) replicates in the respiratory tract of horses, after which infected leukocytes transport virus throughout the body, resulting in abortion or nervous system disorders. Two EHV1 strains circulate in the field: neurovirulent and non-neurovirulent. To investigate differences in replication in the upper respiratory tract (URT), an experimental inoculation study in ponies was performed with both strains. Two groups of six ponies, were inoculated intranasally with 10 6.5 TCID 50 of either strain. Clinical signs, nasal shedding and viremia were evaluated. At early time points post inoculation (pi), one pony of each group was euthanized. Tissues were collected for titration and immunostainings. Number and size of EHV1-induced plaques were calculated, and individual EHV1-infected cells were quantified and characterized. Inoculation with either strain resulted in nasal shedding and replication in several tissues of the URT. Both strains replicated in a plaquewise manner in epithelium of the nasal mucosa, but replication in epithelium of the nasopharynx was largely limited to nonneurovirulent EHV1. Plaques were never able to cross the basement membrane, but individual infected cells were noticed in the connective tissue of all examined tissues for both strains. The total number of these cells however, was 3-7 times lower with non-neurovirulent EHV1 compared to neurovirulent EHV1. CD172a + cells and CD5+ lymphocytes were important target cells for both strains. Interestingly, in lymph nodes, B-lymphocytes were also important target cells for EHV1, irrespective of the strain. Viremia was detected very early pi and infected cells were mainly CD172a + for both strains. In summary, these results are valuable for understanding EHV1 pathogenesis at the port of entry, the URT.

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“…[17][18][19] In vitro and in vivo, DC were used as a cellular vaccine to induce protective and therapeutic antitumour or antiviral immunity. [20][21][22][23] Pilot experiments in human trials showed the induction of antitumour immune responses and even tumour regression after DC vaccination in patients with non-Hodgkin's lymphoma and melanoma. 24,25 Additional approaches demonstrated that DC may also be applied to suppress immune responses via T regulatory cells.…”

Section: Introductionmentioning

confidence: 99%

Monocyte‐derived dendritic cells from horses differ from dendritic cells of humans and mice

2006

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SummaryDendritic cells (DC) are the initiators of immune responses and are present in most tissues in vivo. To generate myeloid DC from monocytes (MoDC) in vitro the necessary cytokines are granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Using degenerated primers delineated from other species and rapid amplification of cDNA ends reverse transcription-polymerase chain reaction (RACE RT-PCR), the cDNA of equine (eq.) GM-CSF was cloned and found to have a point deletion at the 3 0 -end of eq.GM-CSF, resulting in a 24-nucleotide extended open reading frame not described in any species thus far. For differentiating eq.MoDC, monocytes were stimulated with eq.GM-CSF and eq.IL-4. The eq.MoDC was analysed by both light and electron microscopy and by flow cytometry and mixed lymphocyte reaction. The eq.MoDC obtained had the typical morphology and function of DC, including the ability to stimulate allogeneic T cells in a mixed lymphocyte reaction. In contrast to the human system, however, monocytes had to be differentiated for 6-7 days before immature DC were obtained. Our data also indicate that lipopolysaccharide or poly(I:C) alone are not sufficient to confer the full phenotypic transition into mature DC. Thus our study contributes to understanding the heterogeneity of immunity and adds important information on the equine immune system, which is clearly distinct from those of mice or man.

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Dendritic cells presenting equine herpesvirus-1 antigens induce protective anti-viral immunity.

Cited by 16 publications

References 59 publications

Identification of equine herpesvirus-1 antigens recognized by cytotoxic T lymphocytes

Identification of equine herpesvirus-1 antigens recognized by cytotoxic T lymphocytes

Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses

Monocyte‐derived dendritic cells from horses differ from dendritic cells of humans and mice

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