Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice
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- Yu Yu
- Departments of Immunology & Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
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- Dapeng Wang
- Departments of Immunology & Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
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- Chen Liu
- Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL; and
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- Kane Kaosaard
- Departments of Immunology & Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
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- Kenrick Semple
- Departments of Pathology and Cell Biology and
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- Claudio Anasetti
- Departments of Immunology & Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
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- Xue-Zhong Yu
- Departments of Immunology & Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
書誌事項
- 公開日
- 2011-11-03
- DOI
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- 10.1182/blood-2011-03-340315
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>Allogeneic hematopoietic cell transplantation (HCT) is effective therapy for hematologic malignancies through T cell–mediated GVL effects. However, HCT benefits are frequently offset by the destructive GVHD, which is also induced by donor T cells. Naive Th can differentiate into Th1 and Th17 subsets and both can mediate GVHD after adoptive transfer into an allogeneic host. Here we tested the hypothesis that blockade of Th1 and Th17 differentiation is required to prevent GVHD in mice. T cells with combined targeted disruption of T-bet and RORγt have defective differentiation toward Th1 and Th17 and skewed differentiation toward Th2 and regulatory phenotypes, and caused ameliorated GVHD in a major MHC-mismatched model of HCT. GVL effects mediated by granzyme-positive CD8 T cells were largely preserved despite T-bet and RORγt deficiency. These data indicate that GVHD can be prevented by targeting Th1 and Th17 transcription factors without offsetting GVL activity.</jats:p>
収録刊行物
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- Blood
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Blood 118 (18), 5011-5020, 2011-11-03
American Society of Hematology