Selective Blockade of Herpesvirus Entry Mediator–B and T Lymphocyte Attenuator Pathway Ameliorates Acute Graft-versus-Host Reaction

Rio, María-Luisa del; Jones, Nick D.; Bühler, Léo H.; Norris, Paula S.; Shintani, Yasushi; Ware, Carl F.; Rodríguez-Barbosa, José-Ignacio

doi:10.4049/jimmunol.1103698

Cited by 26 publications

(23 citation statements)

References 59 publications

(76 reference statements)

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“…Judging from recent reports (11Y16, 24), the strategy engaging the co-inhibitory pathway may improve allograft survival. Especially, selective BTLA/HVEM blockage, not LIGHT, in graft-versus-host reaction decreased the functional activity of the alloreactive T cells (25). These above reports indicated that the control of BTLA/HVEM/LIGHT pathway may ameliorate alloimmune responses.…”

Section: Discussionmentioning

confidence: 93%

An Agonistic Anti-BTLA mAb (3C10) Induced Generation of IL-10-Dependent Regulatory CD4+ T Cells and Prolongation of Murine Cardiac Allograft

et al. 2014

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Section: Discussionmentioning

confidence: 93%

An Agonistic Anti-BTLA mAb (3C10) Induced Generation of IL-10-Dependent Regulatory CD4+ T Cells and Prolongation of Murine Cardiac Allograft

et al. 2014

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“…Representative sections (spaced 50 m apart) throughout the TG were fixed for 2 h in 4% paraformaldehyde at 4°C, followed by a 30-min incubation in Dako Serum-Free Protein Block. Rat anti-mouse HVEM clone 10F3 antibody (46) was incubated in protein block at 4°C overnight. After three rinses for 5 min each in 1ϫ phosphate-buffered saline (PBS), slides were incubated for 1 h at 25°C with secondary antibody labeled with Alexa Fluor-488 (green) (Invitrogen, Carlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

Interactions between Herpesvirus Entry Mediator (TNFRSF14) and Latency-Associated Transcript during Herpes Simplex Virus 1 Latency

Allen

Rhode-Kurnow

Mott

et al. 2014

J Virol

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f Herpesvirus entry mediator (HVEM) is one of several cell surface proteins herpes simplex virus (HSV) uses for attachment/entry. HVEM regulates cellular immune responses and can also increase cell survival. Interestingly, latency-associated transcript (LAT), the only viral gene consistently expressed during neuronal latency, enhances latency and reactivation by promoting cell survival and by helping the virus evade the host immune response. However, the mechanisms of these LAT activities are not well understood. We show here for the first time that one mechanism by which LAT enhances latency and reactivation appears to be by upregulating HVEM expression. HSV-1 latency/reactivation was significantly reduced in Hvem ؊/؊ mice, indicating that HVEM plays a significant role in HSV-1 latency/reactivation. Furthermore, LAT upregulated HVEM expression during latency in vivo and also when expressed in vitro in the absence of other viral factors. This study suggests a mechanism whereby LAT upregulates HVEM expression potentially through binding of two LAT small noncoding RNAs to the HVEM promoter and that the increased HVEM then leads to downregulation of immune responses in the latent microenvironment and increased survival of latently infected cells. Thus, one of the mechanisms by which LAT enhances latency/reactivation appears to be through increasing expression of HVEM.

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“…GVHD is an immunologic syndrome affecting transplant recipients in which engrafted donor T cells attack host tissues, causing rampant damage (140). Investigators have had success in decreasing symptoms of GVHD in mice by targeting both BTLA-HVEM and LIGHT-HVEM interactions with blocking antibodies (137)(138)(139). Blockade of LIGHT-HVEM signaling has also been shown to increase the rate of survival of solid allografts, including pancreatic islets and cardiac transplants (141,142).…”

Section: Hvem Signaling Impacts a Variety Of Human Diseases Offeringmentioning

confidence: 99%

“…However, HVEM is implicated in a wide range of autoimmune, inflammatory, and infectious processes that impact an astonishing diversity of human syndromes (24). Because of this, the HVEM signaling network is a rich area of research for the discovery of new therapies.Levels of soluble HVEM are elevated in the sera of patients with allergic asthma, rheumatoid arthritis (RA), and atopic dermatitis (135), but HVEM/LIGHT/BTLA signaling and therapeutic opportunities within that network have been most extensively studied in models of graft-versus-host disease (GVHD) (64,74,(136)(137)(138)(139). GVHD is an immunologic syndrome affecting transplant recipients in which engrafted donor T cells attack host tissues, causing rampant damage (140).…”

mentioning

confidence: 99%

Herpesvirus Entry Mediator and Ocular Herpesvirus Infection: More than Meets the Eye

Edwards

Longnecker

2017

J Virol

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As its name suggests, the host receptor herpesvirus entry mediator (HVEM) facilitates herpes simplex virus (HSV) entry through interactions with a viral envelope glycoprotein. HVEM also bridges several signaling networks, binding ligands from both tumor necrosis factor (TNF) and immunoglobulin (Ig) superfamilies with diverse, and often opposing, outcomes. While HVEM was first identified as a viral entry receptor for HSV, it is only recently that HVEM has emerged as an important host factor in immunopathogenesis of ocular HSV type 1 (HSV-1) infection. Surprisingly, HVEM exacerbates disease development in the eye independently of entry. HVEM signaling has been shown to play a variety of roles in modulating immune responses to HSV and other pathogens, and there is increasing evidence that these effects are responsible for HVEM-mediated pathogenesis in the eye. Here, we review the dual branches of HVEM function during HSV infection: entry and immunomodulation. HVEM is broadly expressed; intersects two important immunologic signaling networks; and impacts autoimmunity, infection, and inflammation. We hope that by understanding the complex range of effects mediated by this receptor, we can offer insights applicable to a wide variety of disease states.KEYWORDS HVEM, herpes simplex virus, herpes stromal keratitis H erpes simplex virus 1 (HSV-1) infects the majority of the world's population by adulthood and is responsible for the vast majority of ocular herpesvirus infections (1-3). In humans and mice, HSV-1 establishes lifelong latency in the trigeminal ganglia (TG) (4,5). Reactivations of HSV-1 in the TG can lead to anterograde movement of the virus along the ophthalmic branch of the trigeminal nerve, resulting in recurrent infection of virtually all the superficial tissues of the eye, including the cornea, conjunctiva, and eyelid (6-8). Ocular herpesvirus infections can lead to epithelial ulceration of the cornea, uveitis, and retinitis but most commonly cause herpes stromal keratitis, or HSK (9). HSK is characterized by chronic inflammation of the corneal stroma, leading to corneal thickening, opacification, scarring, and, potentially, blindness (10, 11). While reactivation accounts for the majority of human disease, most murine studies of HSK model primary infection as mice do not efficiently or reliably reactivate from latency (6).In the primary murine model of HSK, actively replicating HSV-1 in the cornea is detectable by plaque assay for up to 5 to 6 days postinfection (dpi) (9,12). Viral replication initiates HSK, as UV-inactivated or replication-deficient mutant HSV fail to induce HSK in BALB/c mice (13). However, HSK is an inflammatory disease, brought about by host infiltrates, particularly CD4 ϩ T cells and polymorphonuclear cells (PMN), that invade the murine cornea several days after replicating virus has been cleared and that persist chronically (14)(15)(16)(17)(18). A dizzying array of cytokines, chemokines, and immune cell types have been implicated in the pathogenesis of HSK, the temporal and...

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Selective Blockade of Herpesvirus Entry Mediator–B and T Lymphocyte Attenuator Pathway Ameliorates Acute Graft-versus-Host Reaction

Cited by 26 publications

References 59 publications

An Agonistic Anti-BTLA mAb (3C10) Induced Generation of IL-10-Dependent Regulatory CD4+ T Cells and Prolongation of Murine Cardiac Allograft

An Agonistic Anti-BTLA mAb (3C10) Induced Generation of IL-10-Dependent Regulatory CD4+ T Cells and Prolongation of Murine Cardiac Allograft

Interactions between Herpesvirus Entry Mediator (TNFRSF14) and Latency-Associated Transcript during Herpes Simplex Virus 1 Latency

Herpesvirus Entry Mediator and Ocular Herpesvirus Infection: More than Meets the Eye

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