Intervention with costimulatory pathways as a therapeutic approach for graft-versus-host disease

Kwon, Byungsuk

doi:10.3858/emm.2010.42.10.071

Cited by 10 publications

(15 citation statements)

References 74 publications

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“…In addition to the interaction between the T‐cell receptor and MHC, T‐cell activation requires signaling between costimulatory molecules such as CD28 (present on the T cell) and B7.1 or B7.2 (CD80 or CD86, present on the APC); other T‐cell:APC costimulatory signaling pairs include inducible costimulator (ICOS) (CD278):B7H (CD275), OX40 (CD134):OX40L (CD252), CD40L (CD154):CD40, and 4‐1BB (CD137):glucocorticoid‐induced tumor necrosis factor receptor (GITR) [15]. The absence of these costimulatory signals, particularly CD28:B7.1/B7.2, can lead to anergy; furthermore, this interaction can be blocked by coinhibitory molecules such as CTLA4 (CD152), which competes with CD28 for B7.1/B7.2.…”

Section: Pathophysiologymentioning

confidence: 99%

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Concise Review: Acute Graft-Versus-Host Disease: Immunobiology, Prevention, and Treatment

Sung

Chao

2012

Stem Cells Translational Medicine

109

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Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (AHSCT) associated with significant morbidity and mortality. This review focuses on the pathophysiology, clinical features, prevention, and treatment of acute GVHD. Specifically, we explain how new discoveries in immunology have expanded our understanding of GVHD, in which tissue damage from chemotherapy or radiation results in cytokine release, which activates T cells, resulting in proliferation and differentiation, trafficking to target organs, and tissue destruction and inflammation. Insights into the mechanisms of this disease relate directly to the development of preventive strategies and therapies, such as immunosuppression, T-cell depletion, calcineurin inhibitors, CCR5 antagonists, gut decontamination, extracorporeal photopheresis, and more. We also discuss how GVHD affects the gut, liver, and skin, as well as diagnosis, grading, and scoring. We end by examining future directions of treatment, including new immunomodulators and biomarkers. Understanding the immunobiology of GVHD and developing effective preventions and treatments are critical to the continuing success of AHSCT. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:25-32

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Section: Pathophysiologymentioning

confidence: 99%

“…Programmed death‐1 (PD‐1) (CD279):programmed death ligand 1 (B7H1, CD274) are another pair of inhibitory molecules that can induce anergy or tolerance. Models that block these costimulatory or coinhibitory interactions have been shown to reduce or exacerbate GVHD, suggesting possible therapeutic targets [15].…”

Section: Pathophysiologymentioning

confidence: 99%

Concise Review: Acute Graft-Versus-Host Disease: Immunobiology, Prevention, and Treatment

Sung

Chao

2012

Stem Cells Translational Medicine

109

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“…T-cell activation also requires signaling between costimulatory molecules such as CD28 (T cell) and B7.1 or B7.2 (CD80 or CD86, APC); other T-cell:APC pairs include inducible costimulator (ICOS) (CD278):B7H (CD275), OX40 (CD134):OX40L (CD252), CD40L (CD154):CD40, and 4-1BB (CD137):glucocorticoid-induced tumor necrosis factor receptor (GITR) [11]. Absence of costimulatory signals, particularly CD28:B7.1/B7.2, can lead to anergy; furthermore, this interaction can be blocked by coinhibitory molecules such as CTLA4 (CD152), which competes with CD28 for B7.1/B7.2.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Programmed death-1 (PD-1) (CD279): programmed death ligand 1 (PD-L1) (B7H1, CD274) are another pair of inhibitory molecules that can induce anergy or tolerance. Models that block these costimulatory or coinhibitory interactions have been shown to reduce or exacerbate GVHD, suggesting possible therapeutic targets [11]. …”

Section: Pathophysiologymentioning

confidence: 99%

Acute graft-versus-host disease: Are we close to bringing the bench to the bedside?

Sung

Chao

2013

Best Practice & Research Clinical Haematology

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Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (AHSCT) associated with significant morbidity and mortality. This review focuses on the pathophysiology, prevention, and treatment of acute GVHD. Specifically, we explain how new discoveries in immunology have expanded our understanding of GVHD, in which tissue damage from chemotherapy or radiation results in cytokine release, activating T cells, resulting in proliferation and differentiation, trafficking to target organs, and tissue destruction and inflammation. Insights into the mechanisms of this disease relate directly to the development of preventive strategies and therapies, such as immunosuppression, calcineurin inhibitors, T-cell depletion, CCR5 antagonists, gut decontamination, extracorporeal photopheresis, and more. Understanding the immunobiology of GVHD and developing effective preventions and treatments are critical to the continuing success of AHSCT.

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“…T cell co-stimulation has been intensely studied in GVHD (26, 27). Previous work has employed blocking antibodies to receptor or ligand (28, 29), knockout donor T cells (30), or hosts which are deficient for co-stimulatory ligands (31, 32).…”

Section: Introductionmentioning

confidence: 99%

Host-Derived CD70 Suppresses Murine Graft-versus-Host Disease by Limiting Donor T Cell Expansion and Effector Function

Leigh

O'Neill

et al. 2017

The Journal of Immunology

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Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to T cell receptor signaling, co-stimulatory pathways are involved in T cell activation. CD27 is a TNF receptor family member expressed on T cells and its ligand, CD70, is expressed on APCs. The CD27/CD70 co-stimulatory pathway was shown to be critical for T cell function and survival in viral infection models. However, the role of this pathway in allo-HCT is previously unknown. In this study, we have examined its contribution in GVHD pathogenesis. Surprisingly, antibody blockade of CD70 following allo-HCT significantly increases GVHD. Interestingly, while donor T cell- or BM-derived CD70 plays no role in GVHD, host-derived CD70 inhibits GVHD as CD70-/- hosts show significantly increased GVHD. This is evidenced by reduced survival, more severe weight loss, and increased histopathologic damage compared to WT hosts. In addition, CD70-/- hosts have higher levels of proinflammatory cytokines TNF-α, IFN-γ, IL-2, and IL-17. Moreover, accumulation of donor CD4+ and CD8+ effector T cells is increased in CD70-/- versus WT hosts. Mechanistic analyses suggest that CD70 expressed by host hematopoietic cells is involved in the control of alloreactive T cell apoptosis and expansion. Together, our findings demonstrate that host CD70 serves as a unique negative regulator of allogeneic T cell response by contributing to donor T cell apoptosis and inhibiting expansion of donor effector T cells.

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Intervention with costimulatory pathways as a therapeutic approach for graft-versus-host disease

Cited by 10 publications

References 74 publications

Concise Review: Acute Graft-Versus-Host Disease: Immunobiology, Prevention, and Treatment

Concise Review: Acute Graft-Versus-Host Disease: Immunobiology, Prevention, and Treatment

Acute graft-versus-host disease: Are we close to bringing the bench to the bedside?

Host-Derived CD70 Suppresses Murine Graft-versus-Host Disease by Limiting Donor T Cell Expansion and Effector Function

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