BTLA/HVEM Signaling: Milestones in Research and Role in Chronic Hepatitis B Virus Infection

B- and T-lymphocyte attenuator (BTLA) is an immune-regulatory receptor, similar to CTLA-4 and PD-1, and is mainly expressed on B-, T-, and all mature lymphocyte cells. Herpes virus entry mediator (HVEM)-BTLA plays a critical role in immune tolerance and immune responses which are areas of intense research. However, the mechanisms of the BTLA and the BTLA/HVEM signaling pathway in human diseases remain unclear. This review describes the research milestones of BTLA and HVEM in chronological order and their role in chronic HBV infection.

• Publication year

  2019

• Venue

  Frontiers in Immunology

• Publication date

  2019-03-29

• Fields of study

  Medicine

• Identifiers
  DOI 10.3389/fimmu.2019.00617PMID 30984188PMCID 6449624
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2019cited by this paper
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  2019cited by this paper
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  2018cited by this paper
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  2018cited by this paper
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  2018cited by this paper
• Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

  2017cited by this paper
• Hepatic expansion of virus-specific CD8+BTLA+ T cells with regulatory properties in chronic hepatitis B virus infection.

  2017cited by this paper
• Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

  2017cited by this paper
• Age-related changes in the gene expression profile of antigen-specific mouse CD8+ T cells can be partially reversed by blockade of the BTLA/CD160 pathways during vaccination

  2016cited by this paper
• Acute on Chronic Liver Failure-What is in a 'Definition'?

  2016cited by this paper
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  2016cited by this paper
• Immune checkpoint inhibitors: a patent review (2010-2015)

  2016cited by this paper
• Cutting Edge: The BTLA–HVEM Regulatory Pathway Interferes with Protective Immunity to Intestinal Helminth Infection

  2015cited by this paper
• Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis.

  2015cited by this paper
• BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine

  2015cited by this paper
• [The guideline of prevention and treatment for chronic hepatitis B: a 2015 update].

  2015cited by this paper
• An Agonistic Anti-BTLA mAb (3C10) Induced Generation of IL-10-Dependent Regulatory CD4+ T Cells and Prolongation of Murine Cardiac Allograft

  2014cited by this paper
• BTLA, a key regulator of Vγ9Vδ2 T-cell proliferation

  2013cited by this paper
• The co-inhibitory pathway and cellular immune imbalance in the progress of HBV infection

  2013cited by this paper
• BTLA as a biomarker and mediator of sepsis-induced immunosuppression

  2013cited by this paper
• Sirolimus-based regimen promotes inhibitory costimulatory signal of HVEM/BTLA/CD160/LIGHT pathway in allo-renal recipients.

  2013cited by this paper
• The inhibitory receptor BTLA controls γδ T cell homeostasis and inflammatory responses.

  2013cited by this paper
• B- and T-lymphocyte attenuator/herpes virus entry mediator as early indicators for acute rejection following kidney transplantation.

  2013cited by this paper
• CD8 T Cell Memory to a Viral Pathogen Requires Trans Cosignaling between HVEM and BTLA

  2013cited by this paper
• CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells

  2013cited by this paper
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  2013cited by this paper
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  2012influential reference
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  2012cited by this paper
• CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1.

  2012cited by this paper
• B and T Lymphocyte Attenuator Mediates Inhibition of Tumor-Reactive CD8+ T Cells in Patients After Allogeneic Stem Cell Transplantation

  2012cited by this paper
• Expression of B and T lymphocyte attenuator (BTLA) in macrophages contributes to the fulminant hepatitis caused by murine hepatitis virus strain-3

  2012cited by this paper
• BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction

  2012cited by this paper
• Intrahepatic Expression of Programmed Death-1 and its Ligands in Patients with HBV-Related Acute-on-Chronic Liver Failure

  2012cited by this paper
• The Role of Coinhibitory Signaling Pathways in Transplantation and Tolerance

  2012cited by this paper
• Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice.

  2011cited by this paper
• Costimulatory pathways in transplantation

  2011cited by this paper
• B and T lymphocyte attenuator down-regulation by HIV-1 depends on type I interferon and contributes to T-cell hyperactivation.

  2011cited by this paper
• The signaling networks of the herpesvirus entry mediator (TNFRSF14) in immune regulation

  2011cited by this paper
• Regulation of inflammation, autoimmunity, and infection immunity by HVEM‐BTLA signaling

  2011cited by this paper
• Dichotomous regulation of GVHD through bidirectional functions of the BTLA-HVEM pathway.

  2011cited by this paper
• Putting the brakes on BTLA in T cell-mediated cancer immunotherapy.

  2010cited by this paper
• B and T Lymphocyte Attenuator Is Highly Expressed on CMV-Specific T Cells during Infection and Regulates Their Function

  2010cited by this paper
• Slow down and survive: Enigmatic immunoregulation by BTLA and HVEM.

  2010cited by this paper
• HVEM/LIGHT/BTLA/CD160 cosignaling pathways as targets for immune regulation

  2010cited by this paper
• B and T Lymphocyte Attenuator Suppresses IL-21 Production from Follicular Th Cells and Subsequent Humoral Immune Responses

  2010cited by this paper
• Circulating CD4+CD25high Regulatory T Cells and Expression of PD-1 and BTLA on CD4+ T Cells in Patients with Chronic Hepatitis B Virus Infection

  2010cited by this paper
• Detection of protein on BTLAlow cells and in vivo antibody-mediated down-modulation of BTLA on lymphoid and myeloid cells of C57BL/6 and BALB/c BTLA allelic variants.

  2010cited by this paper
• Cutting Edge: B and T Lymphocyte Attenuator Signaling on NKT Cells Inhibits Cytokine Release and Tissue Injury in Early Immune Responses1

  2009cited by this paper
• Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL)

  2009cited by this paper
• B and T Lymphocyte Attenuator Regulates B Cell Receptor Signaling by Targeting Syk and BLNK

  2009cited by this paper
• Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

  2009cited by this paper
• Protective Roles of B and T Lymphocyte Attenuator in NKT Cell-Mediated Experimental Hepatitis

  2009cited by this paper
• Cutting Edge: A Critical Role of B and T Lymphocyte Attenuator in Peripheral T Cell Tolerance Induction 1

  2009cited by this paper
• T Cell Intrinsic Heterodimeric Complexes between HVEM and BTLA Determine Receptivity to the Surrounding Microenvironment1

  2009cited by this paper
• The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T‐cell activation

  2009cited by this paper
• Editorial: Therapeutic potential of targeting BTLA

  2009cited by this paper
• Soluble B and T Lymphocyte Attenuator Possesses Antitumor Effects and Facilitates Heat Shock Protein 70 Vaccine-Triggered Antitumor Immunity against a Murine TC-1 Cervical Cancer Model In Vivo1

  2009cited by this paper
• Regulatory T Cell Expression of Herpesvirus Entry Mediator Suppresses the Function of B and T Lymphocyte Attenuator-Positive Effector T Cells1

  2008influential reference
• CD160 and BTLA: LIGHTs out for CD4+ T cells

  2008cited by this paper
• A crucial role for HVEM and BTLA in preventing intestinal inflammation

  2008cited by this paper
• The Inhibitory HVEM-BTLA Pathway Counter Regulates Lymphotoxin β Receptor Signaling to Achieve Homeostasis of Dendritic Cells1

  2008cited by this paper
• Development of autoimmune hepatitis-like disease and production of autoantibodies to nuclear antigens in mice lacking B and T lymphocyte attenuator.

  2008cited by this paper
• Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages.

  2008cited by this paper
• Interleukin‐6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival

  2007cited by this paper
• Unexpected Role of B and T Lymphocyte Attenuator in Sustaining Cell Survival during Chronic Allostimulation

  2007cited by this paper
• Ligation of B and T Lymphocyte Attenuator Prevents the Genesis of Experimental Cerebral Malaria1

  2007cited by this paper
• Combined Coinhibitory and Costimulatory Modulation with Anti‐BTLA and CTLA4Ig Facilitates Tolerance in Murine Islet Allografts

  2007cited by this paper
• Association of Grb-2 and PI3K p85 with phosphotyrosile peptides derived from BTLA.

  2006cited by this paper
• Association of a BTLA gene polymorphism with the risk of rheumatoid arthritis.

  2006cited by this paper
• Balancing co-stimulation and inhibition with BTLA and HVEM

  2006cited by this paper
• The guideline of prevention and treatment for chronic hepatitis B

  2005cited by this paper
• B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator

  2005influential reference
• B and T Lymphocyte Attenuator Exhibits Structural and Expression Polymorphisms and Is Highly Induced in Anergic CD4+ T Cells 1

  2005cited by this paper
• Attenuating Lymphocyte Activity

  2005cited by this paper
• Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2.

  2003cited by this paper
• BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1

  2003cited by this paper
• [Acute-on-chronic liver failure].

  1995cited by this paper

• The Function of B and T Lymphocyte Attenuator and Its Role in Transplantation

  2025cites this paper
• CD28 Superfamily Costimulatory Molecules in Chronic Pain: Focus on Immunomodulation

  2025cites this paper
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  2025cites this paper
• BTLA: An Emerging Immune Checkpoint Target in Cancer Immunotherapy

  2025cites this paper
• TNFSF14 (LIGHT) in intestinal inflammation: balancing immune activation and resolution in IBD

  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
• Revolutionary Cancer Therapy for Personalization and Improved Efficacy: Strategies to Overcome Resistance to Immune Checkpoint Inhibitor Therapy

  2025cites this paper
• Blockade of BTLA alone or in combination with PD-1 restores the activation and proliferation of CD8+ T cells during in vitro infection with NCP BVDV.

  2024cites this paper
• Contradictory Mechanisms of rheumatoid arthritis and hepatitis B virus infection activation

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  2024influential citation
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  2024cites this paper
• Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer

  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
• Immune checkpoint inhibitors for multiple myeloma immunotherapy

  2023cites this paper
• Causality between Peripheral Immune Cell Counts and Membranous Nephropathy: A Bidirectional Mendelian Randomization Study

  2023cites this paper
• BTLA and HVEM: Emerging players in the tumor microenvironment and cancer progression.

  2023cites this paper
• Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy

  2023cites this paper
• Effects of Circulating Exosomes on B cells in Head and Neck Squamous Cell Carcinoma

  2022cites this paper
• Siglec-5 is an inhibitory immune checkpoint molecule for human T cells

  2022cites this paper
• Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome

  2022influential citation
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  2022cites this paper
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  2022cites this paper
• Targeting the HVEM protein using a fragment of glycoprotein D to inhibit formation of the BTLA/HVEM complex.

  2022cites this paper
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  2022cites this paper
• Characterization of multiple soluble immune checkpoints in individuals with different Mycobacterium tuberculosis infection status and dynamic changes during anti-tuberculosis treatment

  2022cites this paper
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  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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  2021cites this paper
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  2021influential citation
• Detection of Immune Checkpoint Receptors – A Current Challenge in Clinical Flow Cytometry

  2021cites this paper
• Virtual Evolution of HVEM Segment for Checkpoint Inhibitor Discovery

  2021cites this paper
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  2021cites this paper
• Toward a new era of hepatitis B virus therapeutics: The pursuit of a functional cure

  2021cites this paper
• Roles of BTLA in Immunity and Immune Disorders

  2021cites this paper
• Integrative Analysis of the Expression of SIGLEC Family Members in Lung Adenocarcinoma via Data Mining

  2021cites this paper
• Association of BTLA Polymorphisms with Susceptibility to Non-Small-Cell Lung Cancer in the Chinese Population

  2021cites this paper
• Co-inhibitory receptors, transcription factors and tolerance.

  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
• LAG3 (CD223) and autoimmunity: Emerging evidence.

  2020cites this paper
• The expression and immunoregulation of immune checkpoint molecule VISTA in autoimmune diseases and cancers.

  2020cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019influential citation