Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion

Das, Hiranmoy; Imoto, Shion; Murayama, Tohru; Mizuno, Ishikazu; Sugimoto, Tsuneaki; Taniguchi, Rika; Toda, Kyoko; Isobe, Takashi; Nakagawa, Toshio; Nishimura, Ryosei

doi:10.1038/sj.bmt.1702799

Cited by 21 publications

(19 citation statements)

References 29 publications

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“…23,24 Previous studies have shown that elimination of IFN-␥ production magnifies GVHD in lethally irradiated murine allo-HCT recipients. [5][6][7][8][9]12 However, IFN-␥ paradoxically accelerates death in nonirradiated and sublethally irradiated mice receiving allogeneic donor lymph node and spleen cells or purified T cells.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical effects of IFN-γ in graft-versus-host disease reflect promotion of lymphohematopoietic graft-versus-host reactions and inhibition of epithelial tissue injury

Wang¹,

Asavaroengchai²,

Yeap

et al. 2009

Blood

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Section: Discussionmentioning

confidence: 99%

Paradoxical effects of IFN-γ in graft-versus-host disease reflect promotion of lymphohematopoietic graft-versus-host reactions and inhibition of epithelial tissue injury

Wang¹,

Asavaroengchai²,

Yeap

et al. 2009

Blood

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“…The G allele is the known high-expressing allele, and high levels of IL2 have been described to correlate with severity of acute GVHD. 32,36 A previous study from North America on a cohort of similar time frame to our screening cohort 32 reported an association between the recipient IL2-330 G allele and acute GVHD as well as a trend toward risk of chronic GVHD. In our study, we found an association of the GT genotype with risk of chronic GVHD.…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study

Harkensee

Oka

Onizuka

et al. 2012

Blood

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“…73 Therefore, the effects of IFN-␥ production and signaling after SCT are highly dependent on variables, such as conditioning regimen, the balance of intermediate molecules invoked, and the GVHD target organs involved. Whereas cause-andeffect studies in clinical BMT are extremely difficult, multiple studies using both genotyping 81 and mRNA analysis 82,83 have correlated cytokine induction to severe acute and chronic GVHD. Unfortunately, these studies were too small or did not attempt to dissect organ-specific effects.…”

Section: Type I Ifnmentioning

confidence: 99%

The interferon-dependent orchestration of innate and adaptive immunity after transplantation

Robb

Hill

2012

Blood

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The therapeutic GVL effect after allogeneic stem cell transplantation is limited by the development of GVHD. The ultimate aim of current research is to separate the 2 processes in a meaningful fashion. The IFNs are a pleiotropic group of cytokines that were originally recognized because of their ability to interfere with viral replication. However, it is now established that these cytokines play an important role in orchestrating both innate and adaptive immunity. Multiple studies have investigated the effects of both types I and II IFN on GVHD and GVL in preclinical transplant models. The results indicate variable effects that are dependent on the period of activity within the developing immune response, the presence and type of pretransplant conditioning and the differential mechanisms, and IntroductionStem cell transplantation (SCT) has been routinely used as curative therapy for hematologic malignancies for more than 3 decades. Although autologous SCT is now principally used as therapy for myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma, allogeneic SCT is more widely used to treat acute and chronic leukemia, myelodysplasia, and advanced lymphoid malignancies failing other modalities. Allogeneic SCT is limited by the consequences of donor immune activation in response to recipient alloantigens, leading to the development of GVHD. GVHD occurs in the majority of recipients of unmanipulated (T cell-replete) grafts 1 and may develop early (in the first 100 days) after SCT (acute) or thereafter (chronic), typically with divergent presentations. The therapeutic potential of stem cell transplantation lies within the GVL effect whereby residual recipient-type malignancy is eradicated by donor NK cells and/or T cells. GVHD and GVL responses are closely related immune-mediated processes and are controlled in large part by cytokines. Our understanding of the IFNs in GVHD and GVL has greatly expanded in the last 5 years, opening the possibility of manipulation for therapeutic gain. Pathophysiology of acute GVHD and GVLAcute GVHD is initiated by recipient tissue inflammation in response to the transplant conditioning or preparative regimen, used typically to eradicate malignancy and inhibit rejection of the transplanted allodisparate graft. This results in production of proinflammatory cytokines, typically IL-1, IL-6, and TNF. 2 The resulting inflammatory environment leads to activation of recipient cells capable of presenting alloantigen to incoming donor T cells. These antigen-presenting cells (APCs) can include both hematopoietic and nonhematopoietic cells. 3,4 Acute GVHD is absolutely dependent on this interaction between APC and donor ␣␤ T cells. 5Although T-cell depletion protects from GVHD, it can also increase graft rejection, inhibit GVL effects, and delay immune reconstitution. Consequently, recipients of allogeneic SCT have a lower risk of relapse than those of syngeneic SCT or T cell-depleted allogeneic SCT. 6 In murine models where donor and recipients are MHC mismatched, both CD4 ϩ and CD8 ϩ T cells con...

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Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion

Cited by 21 publications

References 29 publications

Paradoxical effects of IFN-γ in graft-versus-host disease reflect promotion of lymphohematopoietic graft-versus-host reactions and inhibition of epithelial tissue injury

Paradoxical effects of IFN-γ in graft-versus-host disease reflect promotion of lymphohematopoietic graft-versus-host reactions and inhibition of epithelial tissue injury

Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study

The interferon-dependent orchestration of innate and adaptive immunity after transplantation

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