The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease

Tanaka, Junji; Imamura, Masahiro; Kasai, Masaharu; Hashino, Satoshi; Kobayashi, Shogo; Noto, Satoshi; Higa, Toshio; Sakurada, Keisuke; Asaka, Masahiro

doi:10.1038/sj.bmt.1700708

Cited by 70 publications

(47 citation statements)

References 2 publications

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“…In the murine system, it has been shown that post-thymic CD4 þ T cells are important in inducing cGVHD. 20 In addition, several reports have demonstrated that type 2 cytokines are associated with cGVHD, 21,22 whereas other studies favor the significance of Th1 balance in cGVHD. [23][24][25][26] In this study, we analyzed the cytokine production of T cells in the chronic phase of patients who underwent allo-HSCT and found that IL-4-producing CD8 þ T cells are closely associated with cGVHD.…”

Section: Gvhd; Hsct; Cytokinesmentioning

confidence: 99%

IL-4-producing CD8+ T cells may be an immunological hallmark of chronic GVHD

Nakamura

Amakawa

Takebayashi

et al. 2005

Bone Marrow Transplant

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Summary:Chronic graft-versus-host disease (cGVHD) occurs in approximately 60-80% of those who survive over 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the pathophysiology of cGVHD is poorly understood. To gain more insight into the immunological mechanism of cGVHD, we examine cytokine production of peripheral blood T cells from 19 patients in the chronic phase of allo-HSCT. The percentage of IFN-c-producing CD8 þ T cells among CD8 þ T cells was significantly higher in patients with or without cGVHD than in normal control subjects (Po0.001). On the other hand, the percentage of IL-4-producing CD8 þ T cells among CD8 þ T cells was significantly higher in patients with cGVHD (mean 3.3%; range 1.3-8.2%) than in patients without cGVHD (mean 1.2%; range 0.8-1.7%) and normal control subjects (mean 1.1%; range 0.1-1.6%) (both Po0.001). By contrast, the percentage of IL-4-producing CD4 þ T cells was not different among patients with and without cGVHD and normal controls. These findings suggest that IL-4-producing CD8 þ T cells may be an immunological marker of cGVHD.

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Section: Gvhd; Hsct; Cytokinesmentioning

confidence: 99%

IL-4-producing CD8+ T cells may be an immunological hallmark of chronic GVHD

Nakamura

Amakawa

Takebayashi

et al. 2005

Bone Marrow Transplant

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“…54,55 We also measured the plasma levels of such Th1 cytokines, IL-2, IL-12 and IFN-␥, but these cytokine levels were not associated with the severity of aGVHD.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease

Sakata

Yasui

Okamura

et al. 2001

Bone Marrow Transplant

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Summary:The plasma levels of a panel of cytokines and cytokineassociated molecules (IL-1␣, IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, macrophage colony-stimulating factor (M-CSF), interferon-␥ (IFN-␥), tumor necrosis factor-␣ (TNF-␣), soluble IL-2 receptor (sIL-2R), soluble tumor necrosis factor receptor I or II (sTNFRI or II)) were assessed in 56 plasma samples of 13 pediatric patients undergoing hematopoietic stem cell transplantation (HSCT, bone marrow in 12 and cord blood in one) from unrelated donors. Eight patients developed severe (grade III-IV) acute GVHD (aGVHD). The plasma IL-6, IL-10, M-CSF, sTNFRI and II levels were significantly high in the severe aGVHD group compared to the mild aGVHD group (grade 0-II). The plasma IL-15 level increased transiently in the early period following HSCT and remained high in the severe aGVHD group even after 4 weeks following HSCT. Based on analysis of the correlations between the kinetics of the plasma cytokine levels after HSCT and the clinical manifestations of aGVHD, IL-15 and/or M-CSF were involved in the development of aGVHD, following elevation of the plasma IL-10 and sTNFRI or II levels. These kinetics suggest that IL-10 and sTNFRs worked as suppressor cytokines and seemed to suppress clinical manifestations of aGVHD. Furthermore, it seemed that the plasma ratio of IL-10/sTNFRII from 5 to 12 weeks following HSCT was linked to the poor outcome in the patients with severe aGVHD, suggesting that IL-10 plays an important role in protecting hosts from transplantation-related complications, including GVHD.

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“…Additionally, variations in the IL-10 receptor gene have been examined in Japanese SLE patients. Two RFLPs (G241A and G520A) within the human IL-10 receptor (IL10R) cDNA sequence have been described [13,14]. None of them lead to any amino acid substitutions or showed any difference in genotype frequencies between patients and controls [15].…”

Section: Il-10 and Il-10 Receptormentioning

confidence: 99%

Cytokine Polymorphisms in Systemic Lupus Erythematosus and Sjögren's Syndrome

et al. 2001

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Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are defined genetically as complex diseases where multiple genes are involved in their pathogenesis. Among the genes of interest are those coding for the cytokines, molecules involved in immunoregulation that have been shown to play important roles in these diseases. Whether abnormalities in cytokine production are owing to genetic polymorphisms within the genes themselves is a matter of intensive study. The finding of functional polymorphisms within cytokine genes and their potential association with disease will open new avenues in their treatment.

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The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease

Cited by 70 publications

References 2 publications

IL-4-producing CD8+ T cells may be an immunological hallmark of chronic GVHD

IL-4-producing CD8+ T cells may be an immunological hallmark of chronic GVHD

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease

Cytokine Polymorphisms in Systemic Lupus Erythematosus and Sjögren's Syndrome

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