Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8<sup>+</sup> T cells that induce GVHD without antileukemic effects

Gartlan, Kate H., Markey, Kate A., Varelias, Antiopi, Bunting, Mark D., Koyama, Motoko, Kuns, Rachel D., Raffelt, Neil C., Olver, Stuart D., Lineburg, Katie E., Cheong, Melody, Teal, Bianca E., Lor, Mary, Comerford, Iain, Teng, Michele W. L., Smyth, Mark J., McCluskey, James, Rossjohn, Jamie, Stockinger, Brigitta, Boyle, Glen M., Lane, Steven W., Clouston, Andrew D., McColl, Shaun R., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2015) Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8<sup>+</sup> T cells that induce GVHD without antileukemic effects. Blood, 126 13: 1609-1620. doi:10.1182/blood-2015-01-622662

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Author Gartlan, Kate H.
Markey, Kate A.
Varelias, Antiopi
Bunting, Mark D.
Koyama, Motoko
Kuns, Rachel D.
Raffelt, Neil C.
Olver, Stuart D.
Lineburg, Katie E.
Cheong, Melody
Teal, Bianca E.
Lor, Mary
Comerford, Iain
Teng, Michele W. L.
Smyth, Mark J.
McCluskey, James
Rossjohn, Jamie
Stockinger, Brigitta
Boyle, Glen M.
Lane, Steven W.
Clouston, Andrew D.
McColl, Shaun R.
MacDonald, Kelli P. A.
Hill, Geoffrey R.
Title Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
Publication date 2015-09-24
Year available 2015
Sub-type Article (original research)
DOI 10.1182/blood-2015-01-622662
Open Access Status Not Open Access
Volume 126
Issue 13
Start page 1609
End page 1620
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Abstract 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.
Keyword Hematology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID MC_U117512792
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
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