Tumor necrosis factor- alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease.

Cooke, Kenneth R.; Hill, Geoffrey R.; Crawford, James M.; Bungard, David; Brinson, Yani S.; Delmonte, John; Ferrara, James L.M.

doi:10.1172/jci4285

Cited by 313 publications

(283 citation statements)

References 68 publications

Supporting

Mentioning

261

Contrasting

Unclassified

Order By: Relevance

“…15 The PAMPs, such as lipopolysaccharide (LPS), which is recognized by TLR-4, are released during the chemo-and radiotherapeutic conditioning regimens performed before the infusion of BMT donor cells. 16,17 In this way, the conditioning regimens amplify the secretion of proinflammatory cytokines such as IL-1, TNF-a, [17][18][19] IL-6 20 and other IFN family members in a process described as a 'cytokine storm'.…”

Section: Triggers For Induction Of Gvhdmentioning

confidence: 99%

New perspectives on the biology of acute GVHD

Paczesny

Hanauer

Sun

et al. 2009

Bone Marrow Transplant

158

126

View full text Add to dashboard Cite

The use of allogeneic hematopoietic cell transplantation (HCT) has increased as new techniques have been developed for transplantation in patients who previously would not have been considered HCT candidates. However, its efficacy continued to be limited by the development of frequent and severe acute GVHD. The complex and intricate pathophysiology of acute GVHD is a consequence of interactions between the donor and host innate and adaptive immune responses. Multiple inflammatory molecules and cell types are implicated in the development of GVHD that can be categorized as:(1) triggers that initiate GVHD by therapy-induced tissue damage and the antigen disparities between host and graft tissue; (2) sensors that detect the triggers, that is, process and present alloantigens; (3) mediators such as T-cell subsets (naive, memory, regulatory, Th17 and natural killer T cells) and (4) the effectors and amplifiers that cause damage of the target organs. These multiple inflammatory molecules and cell types that are implicated in the development of GVHD have been described with models that use stepwise cascades. Herein, we provide a novel perspective on the immunobiology of acute GVHD and briefly discuss some of the outstanding questions and limitations of the model systems.

show abstract

Section: Triggers For Induction Of Gvhdmentioning

confidence: 99%

New perspectives on the biology of acute GVHD

Paczesny

Hanauer

Sun

et al. 2009

Bone Marrow Transplant

158

126

View full text Add to dashboard Cite

show abstract

“…A semiquantitative scoring system was used to assess abnormalities associated with GVHD or allograft rejection. [46] Bioluminescence Imaging of Animals Human T cell trafficking in NOD/SCID-β2m null recipients was assessed non-invasively by bioluminescence with an IVIS 100 CCD camera (Xenogen, Alameda, CA, USA) as described. [47,48] Briefly, mice were injected i.p.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice

Nervi

Rettig

Ritchey

et al. 2007

Experimental Hematology

View full text Add to dashboard Cite

Objective-Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Models of immunodeficient mice that consistently and efficiently reconstitute with xenoreactive human T cells would be a valuable tool for the in vivo study of GVHD, as well as other human immune responses.Materials and Methods-We developed a consistent and sensitive model of human GVHD by retro-orbitally injecting purified human T cells into sublethally irradiated NOD/SCID-β2m null recipients. In addition, we characterized for the first time the trafficking patterns and expansion profiles of xenoreactive human T cells in NOD/SCID-β2m null recipients using in vivo bioluminescence imaging.Results-All NOD/SCID-β2m null mice conditioned with 300 cGy of total body irradiation and injected with 1 × 10 7 human T cells exhibited human T cell engraftment, activation, and expansion, with infiltration of multiple target tissues and a subsequent greater than 20% loss of pretransplant body weight. Importantly, histological examination of the GVHD target tissues revealed changes consistent with human GVHD. Furthermore, we also showed by in vivo bioluminescence imaging that the development of lethal GVHD in the NOD/SCID-β2m null recipients was dependent upon the initial retention and early expansion of human T cells in the retroorbital sinus cavity.Conclusion-Our NOD/SCID-β2m null mouse model provides a system to study the pathophysiology of acute GVHD induced by human T cells and aids in the development of more effective therapies for human GVHD.

show abstract

“…In addition, high levels of TNF-a can directly damage the GI tract, thus leading to amplification of the cascade described [17][18][19]. Given that TNF-a appears to enhance acute GVHD on a variety of levels, it is rational to target in treatment of acute GVHD.…”

Section: Introductionmentioning

confidence: 99%

Infliximab for steroid‐refractory acute GVHD: A case series

et al. 2003

View full text Add to dashboard Cite

Acute and chronic graft‐versus‐host disease (GVHD) remain major barriers to successful hematopoietic stem cell transplantation (SCT). TNF‐α has been implicated in the pathogenesis of GVHD and TNF‐α blockade has been explored for treatment of GVHD. The development of a chimeric mouse/human monoclonal antibody (infliximab) which binds to cells producing TNF‐α, allowing for not only the neutralization of TNF‐α but also lysis of the cells producing the TNF‐α, makes this an attractive drug to explore in GVHD. We report on 11 patients with acute GVHD who were treated with infliximab after failing other therapies. The survival was very poor, in keeping with previously published reports of steroid‐refractory acute GVHD. Two patients with severe diarrhea from acute GI GVHD resolved their symptoms after treatment with infliximab. Only these two patients survived. It appears that of all acute GVHD manifestations, gastrointestinal GVHD may be more responsive to treatment with infliximab than others. Caution is recommended when using this agent since it may exacerbate active infections, particularly aspergillosis. Furthermore, we do not know the correct dose or schedule to use with this drug. Given these data, controlled studies assessing dose and timing of administration may be warranted to study infliximab in acute GVHD. Am. J. Hematol. 74:119–124, 2003. © 2003 Wiley‐Liss Inc.

show abstract

Tumor necrosis factor- alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease.

Cited by 313 publications

References 68 publications

New perspectives on the biology of acute GVHD

New perspectives on the biology of acute GVHD

Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice

Infliximab for steroid‐refractory acute GVHD: A case series

Contact Info

Product

Resources

About