Production of IL-10 by alloreactive sibling donor cells and its influence on the development of acute GVHD

Weston, Lyanne; Geczy, Andrew F.; Briscoe, Helen

doi:10.1038/sj.bmt.1705218

Cited by 26 publications

(19 citation statements)

References 19 publications

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Section: Cytokine Polymorphismscontrasting

confidence: 54%

“…65 The cytokine-releasing profile of donor cells in response to recipient alloantigen stimulation has been shown to correlate with the development of acute GVHD, with a high frequency of donor cells producing IL-10 associated with the absence of acute GVHD after myeloablative HSCT. 66 In contrast to the studies noted previously, 62,63 these studies suggest that higher levels of IL-10 in the peritransplantation period confer protection against the subsequent development of GVHD.At the time of the Lin study it was suggested that IL-10 genotyping be included as part of the standard evaluation of a patient being considered for HSCT from an HLA-identical sibling donor. 67 Clearly, given the biologic complexity of IL-10, we need a much better understanding of the functional significance of immune polymorphisms in this gene before this recommendation can be incorporated into clinical practice.…”

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confidence: 50%

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Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation

Mullally

Ritz

2006

Blood

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The last 2 years have seen much excitement in the field of genetics with the identification of a formerly unappreciated level of "structural variation" within the normal human genome. Genetic structural variants include deletions, duplications, and inversions in addition to the recently discovered, copy number variants. Single nucleotide polymorphisms are the most extensively evaluated variant within the genome to date. Combining our knowledge from these studies with our rapidly accumulating understanding of structural variants, it is apparent that the extent of genetic dissimilarity between any 2 individuals is considerable and much greater than that which was previously recognized. Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. With advances in DNA sequencing technology we now have the capacity to perform genome-wide analysis in a high throughput fashion, permitting a detailed genetic analysis of patient and donor prior to transplantation. Understanding the significance of this additional genetic information and applying it in a clinically meaningful way will be one of the challenges faced by transplant clinicians in the future. Introduction Structural variation in the human genomeRecently, much focus has been directed at documenting the extent of normal human genomic variation, particularly in the form of single nucleotide polymorphisms (SNPs; Table 1). In October 2005, phase 1 of the International Hapmap Project was published. 2 This project catalogued more than one million SNPs, genomewide, into a publicly accessible database (www.hapmap.org). Approximately 11 500 of the SNPs recorded in phase 1 are nonsynonymous coding SNPs. Other examples of genomic variation include gene deletions, inverted gene sequences, multiple copy gene duplications, segmental duplications and large-scale copy number variants (CNVs). Each of these structural variants is shown schematically in Figure 1.In the year prior to the Hapmap publication, 2 landmark studies reported that large-scale CNVs are distributed widely throughout the human genome and that a high proportion of these encompass known genes. 3,4 These studies were groundbreaking because they challenged the previously held view that the complete DNA sequences of any 2 individuals are 99.9% identical, the 0.1% difference being largely attributed to SNPs. Subsequently, several studies on CNVs followed, 5-7 culminating in a large international study of the Hapmap population by Redon et al 101 that identified more than 1400 CNVs spanning approximately 12% of the human genome. Even with this comprehensive evaluation, it is likely that this present index of CNVs is far from complete and new variants are continually being discovered. 8 In 2006, 3 studies specifically characterized deletion variants in the human genome. 9-11 Combined, these investigations described ap...

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Section: Cytokine Polymorphismscontrasting

confidence: 54%

contrasting

confidence: 50%

Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation

Mullally

Ritz

2006

Blood

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“…22,23 In humans, it has been shown that a higher number of IL-4 and IL-10 producing cells are associated with the reduced severity or absence of acute GVHD. 24,25 These observations provide an explanation for the possible protective role of Th2 cytokines in acute GVHD. IL-5 is another Th2 cytokine that has a crucial role in the proliferation, differentiation, survival and activation of eosinophils, 1,14,26 and the CD4 þ Th2 cells are known to produce large amounts of IL-5.…”

Section: Discussionmentioning

confidence: 94%

Eosinophilia predicts better overall survival after acute graft-versus-host-disease

Imahashi¹,

Miyamura²,

Seto³

et al. 2009

Bone Marrow Transplant

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The prognostic significance of eosinophilia after allogeneic hematopoietic SCT (HSCT) and the relationship between eosinophilia and acute GVHD are not well studied. We retrospectively analyzed 201 adult patients who underwent their first allogeneic HSCT. Seventy-three (36%) patients developed eosinophilia within the first 100 days after HSCT. Eosinophilia was observed more frequently among those patients with acute GVHD than those without it (48 vs 25%, P ¼ 0.009). However, it was associated with milder acute GVHD and lower incidence of gut and liver acute GVHD. Among patients with acute GVHD, the 3-year OS for patients with and without eosinophilia was 63.4 and 47.2% (P ¼ 0.02), respectively, and 3-year nonrelapse mortality (NRM) was 20.2 and 37.5% (P ¼ 0.01), respectively. Multivariate analysis confirmed that eosinophilia was associated with a better OS (P ¼ 0.03) and lower NRM (P ¼ 0.046) in patients with acute GVHD, whereas it was not associated with a higher relapse rate (P ¼ 0.45). In contrast, eosinophilia was not associated with outcomes in those patients without acute GVHD. In conclusion, eosinophilia was associated with milder acute GVHD and better prognosis among patients with acute GVHD. The pathophysiology behind eosinophilia after allogeneic HSCT remains to be investigated.

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“…31 IL-10 has been shown to be significantly correlated with reduction in the severity of acute GVHD in several human and murine studies. [46][47][48][49] Furthermore, treatment of both mouse and human CD4 ϩ T cells in the presence of IL-10 induced the generation of Tr1 cells, which are important for active induction of peripheral tolerance. 28,29,40 Our data demonstrating a critical requirement for the secretion of IL-10 by donor T cells in reducing acute GVHD after immunization with host-type CD8␣ ϩ DCs are thus consistent with the critical regulatory role of IL-10 and Tr1 in GVHD.…”

Section: Discussionmentioning

confidence: 99%

Immunization with host-type CD8α+ dendritic cells reduces experimental acute GVHD in an IL-10–dependent manner

Toubai

Malter

Tawara

et al. 2010

Blood

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Production of IL-10 by alloreactive sibling donor cells and its influence on the development of acute GVHD

Cited by 26 publications

References 19 publications

Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation

Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation

Eosinophilia predicts better overall survival after acute graft-versus-host-disease

Immunization with host-type CD8α+ dendritic cells reduces experimental acute GVHD in an IL-10–dependent manner

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