Cytokine expression during acute graft-versus-host disease after allogeneic peripheral stem cell transplantation

Ju, Xingzhu; Xu, Bing; Xiao, Zheng; Li, J Y; Chen, L; Lu, Sangwei; Zhen, Huang

doi:10.1038/sj.bmt.1704972

Cited by 41 publications

(38 citation statements)

References 29 publications

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“…Mucosal damage induced by chemotherapy and irradiation allows microbial products such as LPS to enter the systemic circulation and to trigger the production of inflammatory cytokines such as TNF-␣ and IL-12, both of which are important mediators of GVHD. [19][20][21] This early and high-level IL-12 production was shown to be crucial, as elevated IL-12p70 serum levels in the first month after PBSCT turned out to be a strong predictive factor for aGVHD development. 22 However, elevated serum IL-12 levels may also enhance the GVL reaction, because they were shown to be associated with an improved relapse-free survival.…”

Section: Resultsmentioning

confidence: 99%

G-CSF mobilizes slanDCs (6-sulfo LacNAc+ dendritic cells) with a high proinflammatory capacity

Baumeister

Hölig²,

Bornhäuser³

et al. 2007

Blood

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Section: Resultsmentioning

confidence: 99%

G-CSF mobilizes slanDCs (6-sulfo LacNAc+ dendritic cells) with a high proinflammatory capacity

Baumeister

Hölig²,

Bornhäuser³

et al. 2007

Blood

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“…Several studies report that the levels of IL-18 in various transplant models, as well as in kidney transplant patients, correlate with graft failure (19)(20)(21)(22)(23)25). In the present study we addressed the role of IL-18 in islet injury.…”

Section: Role Of Il-18 In Islet Injury: Exogenous or Endogenous Il-18?mentioning

confidence: 99%

“…IL-18 was reported to be a predictive biomarker for delayed graft function in kidney transplantation (21). In addition, IL-18 levels are increased during acute graftversus-host disease in mice (22) and in human stem cell transplantation (23).…”

mentioning

confidence: 99%

Responses of IL-18- and IL-18 receptor-deficient pancreatic islets with convergence of positive and negative signals for the IL-18 receptor

Lewis

Dinarello

2006

Proc. Natl. Acad. Sci. U.S.A.

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Pancreatic islets contain cells that produce IL-18 and cells that express IL-18 receptors. In experimentally induced diabetes, islet failure correlates with IL-18 levels and diabetes is delayed with blockade of endogenous IL-18. We studied islet-derived IL-18 and responses to IL-18 in a mouse model of islet allograft transplantation. In vitro, IL-18-stimulated islets produced nitric oxide, which closely matched islet apoptosis. By neutralizing IL-18 activity with IL-18 binding protein (IL-18BP), we observed that islets produce bioactive IL-18. In vivo, transgenic mice overproducing IL-18BP (IL-18BP-Tg) exhibited delayed hyperglycemia induced by ␤ cell toxic streptozotocin. Similarly, cultured IL-18BP-Tg islets were protected from streptozotocin-induced apoptosis. In the transplant model, islets grafted from WT to IL-18BP-Tg mice achieved prolonged normoglycemia (P ‫؍‬ 0.031). Improved graft function was also observed by using IL-18-deficient islets transplanted into WT recipients, demonstrating that endogenous, islet-derived IL-18 mediates IL-18-driven graft damage. Unexpectedly, islets from mice deficient in IL-18 receptor ␣ chain (IL-18R) exhibited rapid graft failure (P ‫؍‬ 0.024; IL-18-versus IL-18R-deficient grafts in WT recipients). In related studies, IL-18R-deficient splenocytes and macrophages produced 2-to 3-fold greater amounts of IL-18, TNF␣, macrophage inflammatory protein 1, macrophage inflammatory protein 2, and IFN␥ upon stimulation with Con A, Toll-like receptor 2 agonist, or anti-CD3 antibodies. These data reveal a role for islet-derived IL-18 activity during inflammation-mediated islet injury. Importantly, discrepancies between IL-18-and IL-18R-deficient cells suggest that IL-18R␣ chain is used by an inflammationsuppressing signal.diabetes ͉ inflammation ͉ transplantation

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“…In this context, GVHD has been extensively associated with Th1-related cytokines (IFN γ , IL-2, and IL-12) [4, 5] although these are not the only cytokines involved in inflammation. Recently, Th17-related cytokines (IL-17A and IL-17F) have been said to be prominent in solid organ rejection in murine models [6–9] and while their presence is not required for GVHD development, they contribute to exacerbation of this disease [8].…”

Section: Introductionmentioning

confidence: 99%

Role of CD8 Regulatory T Cells versus Tc1 and Tc17 Cells in the Development of Human Graft-versus-Host Disease

Gutiérrez‐Hoya

López‐Santiago

Vela‐Ojeda

et al. 2017

Journal of Immunology Research

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CD8+ T cells that secrete proinflammatory cytokines play a central role in exacerbation of inflammation; however, a new subpopulation of CD8 regulatory T cells has recently been characterized. This study analyzes the prominent role of these different subpopulations in the development of graft-versus-host disease (GVHD). Samples from 8 healthy donors mobilized with Filgrastim® (G-CSF) and 18 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated by flow cytometry. Mobilization induced an increase in Tc1 (p < 0.01), Th1 (p < 0.001), Tc17 (p < 0.05), and CD8+IL-10+ cells (p < 0.05), showing that G-CSF induces both pro- and anti-inflammatory profiles. Donor-patient correlation revealed a trend (p = 0.06) toward the development of GVHD in patients who receive a high percentage of Tc1 cells. Patients with acute GVHD (aGVHD), either active or controlled, and patients without GVHD were evaluated; patients with active aGVHD had a higher percentage of Tc1 (p < 0.01) and Tc17 (p < 0.05) cells, as opposed to patients without GVHD in whom a higher percentage of CD8 Treg cells (p < 0.01) was found. These findings indicate that the increase in Tc1 and Tc17 cells is associated with GVHD development, while regulatory CD8 T cells might have a protective role in this disease. These tests can be used to monitor and control GVHD.

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Cytokine expression during acute graft-versus-host disease after allogeneic peripheral stem cell transplantation

Cited by 41 publications

References 29 publications

G-CSF mobilizes slanDCs (6-sulfo LacNAc+ dendritic cells) with a high proinflammatory capacity

G-CSF mobilizes slanDCs (6-sulfo LacNAc+ dendritic cells) with a high proinflammatory capacity

Responses of IL-18- and IL-18 receptor-deficient pancreatic islets with convergence of positive and negative signals for the IL-18 receptor

Role of CD8 Regulatory T Cells versus Tc1 and Tc17 Cells in the Development of Human Graft-versus-Host Disease

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