T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor
Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which lim...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.761448/full |
| _version_ | 1818721835484708864 |
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| author | Hua Jiang Denggang Fu Alan Bidgoli Sophie Paczesny |
| author_facet | Hua Jiang Denggang Fu Alan Bidgoli Sophie Paczesny |
| author_sort | Hua Jiang |
| collection | DOAJ |
| description | Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occurring more than 2 years after HCT for malignant disease. Graft versus tumor (GVT) is a major component of the overall beneficial effects of allogeneic HCT in the treatment of hematological malignancies. Better understanding of GVHD pathogenesis is important to identify new therapeutic targets for GVHD prevention and therapy. Emerging data suggest opposing roles for different T cell subsets, e.g., IFN-γ producing CD4+ and CD8+ T cells (Th1 and Tc1), IL-4 producing T cells (Th2 and Tc2), IL-17 producing T cells (Th17 and Tc17), IL-9 producing T cells (Th9 and Tc9), IL-22 producing T cells (Th22), T follicular helper cells (Tfh), regulatory T-cells (Treg) and tissue resident memory T cells (Trm) in GVHD and GVT etiology. In this review, we first summarize the general description of the cytokine signals that promote the differentiation of T cell subsets and the roles of these T cell subsets in the pathogenesis of GVHD. Next, we extensively explore preclinical findings of T cell subsets in both GVHD/GVT animal models and humans. Finally, we address recent findings about the roles of T-cell subsets in clinical GVHD and current strategies to modulate T-cell differentiation for treating and preventing GVHD in patients. Further exploring and outlining the immune biology of T-cell differentiation in GVHD that will provide more therapeutic options for maintaining success of allo-HCT. |
| first_indexed | 2024-12-17T20:45:03Z |
| format | Article |
| id | doaj.art-4a3c4f2de5824a368f0fd589a4789403 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T20:45:03Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4a3c4f2de5824a368f0fd589a47894032022-12-21T21:33:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.761448761448T Cell Subsets in Graft Versus Host Disease and Graft Versus TumorHua JiangDenggang FuAlan BidgoliSophie PaczesnyAllogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occurring more than 2 years after HCT for malignant disease. Graft versus tumor (GVT) is a major component of the overall beneficial effects of allogeneic HCT in the treatment of hematological malignancies. Better understanding of GVHD pathogenesis is important to identify new therapeutic targets for GVHD prevention and therapy. Emerging data suggest opposing roles for different T cell subsets, e.g., IFN-γ producing CD4+ and CD8+ T cells (Th1 and Tc1), IL-4 producing T cells (Th2 and Tc2), IL-17 producing T cells (Th17 and Tc17), IL-9 producing T cells (Th9 and Tc9), IL-22 producing T cells (Th22), T follicular helper cells (Tfh), regulatory T-cells (Treg) and tissue resident memory T cells (Trm) in GVHD and GVT etiology. In this review, we first summarize the general description of the cytokine signals that promote the differentiation of T cell subsets and the roles of these T cell subsets in the pathogenesis of GVHD. Next, we extensively explore preclinical findings of T cell subsets in both GVHD/GVT animal models and humans. Finally, we address recent findings about the roles of T-cell subsets in clinical GVHD and current strategies to modulate T-cell differentiation for treating and preventing GVHD in patients. Further exploring and outlining the immune biology of T-cell differentiation in GVHD that will provide more therapeutic options for maintaining success of allo-HCT.https://www.frontiersin.org/articles/10.3389/fimmu.2021.761448/fullgraft versus host diseasegraft versus tumortissue resident memory t cellcell therapyt cells subsets |
| spellingShingle | Hua Jiang Denggang Fu Alan Bidgoli Sophie Paczesny T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor Frontiers in Immunology graft versus host disease graft versus tumor tissue resident memory t cell cell therapy t cells subsets |
| title | T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor |
| title_full | T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor |
| title_fullStr | T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor |
| title_full_unstemmed | T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor |
| title_short | T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor |
| title_sort | t cell subsets in graft versus host disease and graft versus tumor |
| topic | graft versus host disease graft versus tumor tissue resident memory t cell cell therapy t cells subsets |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.761448/full |
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