Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects
| Autor: | Bianca E. Teal, Mark J. Smyth, Katie E. Lineburg, Kate A. Markey, Glen M. Boyle, Shaun R. McColl, Neil C. Raffelt, Antiopi Varelias, Mark D. Bunting, James McCluskey, Motoko Koyama, Jamie Rossjohn, Mary Lor, Brigitta Stockinger, Kelli P. A. MacDonald, Geoffrey R. Hill, Steven W. Lane, Rachel D. Kuns, Stuart D. Olver, Melody Cheong, Michele W.L. Teng, Iain Comerford, Andrew D. Clouston, Kate H. Gartlan |
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| Rok vydání: | 2015 |
| Předmět: |
Graft-vs-Leukemia Effect
CD8 Antigens Immunology Population Graft vs Host Disease Graft vs Leukemia Effect CD8-Positive T-Lymphocytes Biology Biochemistry Proinflammatory cytokine immune system diseases medicine Animals Humans Cytotoxic T cell education Bone Marrow Transplantation Mice Inbred BALB C education.field_of_study Interleukin-17 Cell Biology Hematology medicine.disease Mice Inbred C57BL Transplantation surgical procedures operative Graft-versus-host disease Th17 Cells Female Stem cell CD8 Stem Cell Transplantation |
| Zdroj: | Blood. 126:1609-1620 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2015-01-622662 |
| Popis: | IL-17-producing cells are important mediators of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). Here we demonstrate that a distinct CD8(+) Tc17 population develops rapidly after SCT but fails to maintain lineage fidelity such that they are unrecognizable in the absence of a fate reporter. Tc17 differentiation is dependent on alloantigen presentation by host dendritic cells (DCs) together with IL-6. Tc17 cells express high levels of multiple prototypic lineage-defining transcription factors (eg, RORγt, T-bet) and cytokines (eg, IL-17A, IL-22, interferon-γ, granulocyte macrophage colony-stimulating factor, IL-13). Targeted depletion of Tc17 early after transplant protects from lethal acute GVHD; however, Tc17 cells are noncytolytic and fail to mediate graft-versus-leukemia (GVL) effects. Thus, the Tc17 differentiation program during GVHD culminates in a highly plastic, hyperinflammatory, poorly cytolytic effector population, which we term "inflammatory iTc17" (iTc17). Because iTc17 cells mediate GVHD without contributing to GVL, therapeutic inhibition of iTc17 development in a clinical setting represents an attractive approach for separating GVHD and GVL. |
| Databáze: | OpenAIRE |
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