ArticleBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation2008
Th2 cell therapy of established acute graft-versus-host disease requires IL-4 and IL-10 and is abrogated by IL-2 or host-type antigen-presenting cells.
Article in Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- A donor thrombomodulin gene variation predicts graft-versus-host disease development and mortality after bone marrow transplantation.International journal of hematology · 2015Trial
- Sibling donor and recipient immune modulation with atorvastatin for the prophylaxis of acute graft-versus-host disease.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- Trial
- The Role of the Gut Microbiota in Allogeneic Hematopoietic Cell Transplantation.American journal of hematology · 2026Review
- Article
- Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice.Biomarker research · 2024Review
- CARs: a new approach for the treatment of autoimmune diseases.Science China. Life sciences · 2023Review
- T Helper Cell Lineage-Defining Transcription Factors: Potent Targets for Specific GVHD Therapy?Frontiers in immunology · 2021Review
- MicroRNA-155 Modulates Acute Graft-versus-Host Disease by Impacting T Cell Expansion, Migration, and Effector Function.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- In vivo IL-4 prevents allo-antigen driven CD8Clinical immunology (Orlando, Fla.) · 2017Article
- Targeting Cytokines in GVHD Therapy.Journal of immunology research and therapy · 2017Article
- GRIM19 ameliorates acute graft-versus-host disease (GVHD) by modulating Th17 and Treg cell balance through down-regulation of STAT3 and NF-AT activation.Journal of translational medicine · 2016Article
- High-Dose Sirolimus and Immune-Selective Pentostatin plus Cyclophosphamide Conditioning Yields Stable Mixed Chimerism and Insufficient Graft-versus-Tumor Responses.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers.Bone marrow transplantation · 2014Review
- Rapamycin-resistant effector T-cell therapy.Immunological reviews · 2014Review
- Identification of gene microarray expression profiles in patients with chronic graft-versus-host disease following allogeneic hematopoietic cell transplantation.Clinical immunology (Orlando, Fla.) · 2013Article
- A molecular and computational diagnostic approach identifies FOXP3, ICOS, CD52 and CASP1 as the most informative biomarkers in acute graft-versus-host disease.Haematologica · 2012Article
- Plasma level of lipopolysaccharide-binding protein is indicative of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.International journal of hematology · 2012Article
- Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease.Journal of leukocyte biology · 2012Article
- Generation and large-scale expansion of human inducible regulatory T cells that suppress graft-versus-host disease.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Delayed donor Th2 cell infusion permits a graft-versus-tumor (GVT) effect to occur with subsequent amelioration of established graft-versus-host disease (GVHD). Relative to GVHD controls (B6-into-BALB/c model), recipients of delayed Th2 cells (day 14 post-BMT) had increased survival (3/3 experiments [exp]; each exp P < .0001) and reduced GVHD by histology analysis 5 days post-Th2 infusion without increased tumor burden (3 of 3 exp; each exp P < or = .02). Th2 cell-mediated amelioration of GVHD was associated with greatly reduced allospecific IFN-gamma secretion, in vivo augmentation of allospecific IL-4 and IL-10 secretion, and reduction in donor CD8(+) T cell number post-BMT (3 of 3 exp; each comparison, P < or = .003). To better understand the molecular mechanism of this GVHD therapy, Th2 cells were generated from wild-type (WT), IL-4 deficient (KO), or IL-10 KO donors: remarkably, recipients of IL-4 or IL-10 KO Th2 cells had no survival advantage, no improvement in GVHD by histology, no reduction in CD8(+) T cell expansion post-BMT, and no in vivo shift toward type II cytokines. We reasoned that IL-2 and alloantigen availability may be limiting factors for Th2 cell therapy, and as such, evaluated whether coadministration of IL-2 or coinfusion of host-type antigen-presenting cells (APC) might intensify the anti-GVHD effect. However, contrary to these hypotheses, concomitant IL-2 therapy or APC administration fully abrogated the Th2 cell-mediated survival advantage and histology-defined GVHD reduction, reduced Th2 cell expansion in vivo while promoting CD8(+) T cell expansion from cells originating from the initial allograft, and impaired type II polarization in vivo. In conclusion, Th2 cell therapy can rapidly ameliorate severe GVHD via IL-4 and IL-10 mediated mechanisms, and potentially, via IL-2 consumption and APC modulation mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.