Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects.

@article{Gartlan2015Tc17CA,
  title={Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects.},
  author={Kate H. Gartlan and Kate A. Markey and Antiopi Varelias and Mark D. Bunting and Motoko Koyama and Rachel D. Kuns and Neil C. Raffelt and Stuart D. Olver and Katie E. Lineburg and Melody Cheong and Bianca E. Teal and Mary Lor and Iain Comerford and Michele W. L. Teng and Mark J. Smyth and James McCluskey and Jamie Rossjohn and Brigitta Stockinger and Glen M. Boyle and Steven W. Lane and Andrew D. Clouston and Shaun R. McColl and Kelli P A MacDonald and Geoffrey R. Hill},
  journal={Blood},
  year={2015},
  volume={126 13},
  pages={
          1609-20
        }
}
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… 
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Correlation of Tc17 cells at early stages after allogeneic hematopoietic stem cell transplantation with acute graft-versus-host disease.
Th17 plasticity and transition toward a pathogenic cytokine signature are regulated by cyclosporine after allogeneic SCT.
TLDR
Th17 polarization and ensuing differentiation are mediated by sequential inflammatory signals, which are modulated by immunosuppressive therapy, leading to distinct phenotypes within this lineage.
Donor T-cell-derived GM-CSF drives alloantigen presentation by dendritic cells in the gastrointestinal tract.
TLDR
It is demonstrated that although GM-CSF-secreting Th17 and non-Th17 cells expanded in the colon over time after SCT, the Th17 lineage expanded to represent 10% to 20% of the GM- CSF secreting T cells at this site by 4 weeks, suggesting that GM-csF inhibition may be a tractable clinical intervention to limit donor alloantigen presentation and GVHD in the lower gastrointestinal tract.
Flt-3L Expansion of Recipient CD8α+ Dendritic Cells Deletes Alloreactive Donor T Cells and Represents an Alternative to Posttransplant Cyclophosphamide for the Prevention of GVHD
TLDR
Pre-transplant Flt-3L therapy is highlighted as a potent new therapeutic strategy to delete alloreactive T cells and prevent GVHD, which appears particularly well suited to haploidentical BMT where the control of infection and the prevention of GV HD are paramount.
IL-22-dependent dysbiosis and mononuclear phagocyte depletion contribute to steroid-resistant gut graft-versus-host disease in mice
TLDR
It is shown that the pathogenesis of SR-Gut-aGVHD is associated with reduction of IFN-γ+ Th/Tc1 cells and preferential expansion of IL-17−IL-22+ Th-c22 cells, and the potential efficacy of Il-22 antagonists and IFn-γ agonists in SR-gut- aGVHD therapy is suggested.
IL-6 dysregulation originates in dendritic cells and initiates graft-versus-host disease via classical signaling.
TLDR
It is demonstrated that IL-6 secretion from recipient dendritic cells (DC) initiates the systemic dysregulation of this cytokine, highlightingIL-6 classical-signaling and downstream Th17/Th22 differentiation as key therapeutic targets after alloSCT.
Murine allogeneic CD19 CAR T cells harbor potent antileukemic activity but have the potential to mediate lethal GVHD.
TLDR
It is demonstrated that donor-derived allogeneic CAR T cells are active but have the capacity to drive GVHD.
Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome.
TLDR
It is demonstrated that stem cell transplant recipients lacking the ability to generate or signal IL-17 develop intestinal hyper-acute GVHD, consistent with an additional protective role for this cytokine independent of effects on dysbiosis.
Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells.
TLDR
This work has used a highly translational nonhuman primate model to interrogate the transcriptional signature of T cells during breakthrough acute graft-versus-host disease (GVHD) that occurs in the setting of clinically relevant immune suppression and compared this to the hyperacute GVHD, which develops in unprophylaxed or suboptimally prophylactic transplant recipients.
IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation
TLDR
It is demonstrated that IL-17C deficiency in the graft significantly promoted alloreactive T cell responses and induced aggravated aGVHD compared with wildtype donors in a fully MHC-mismatched allo-HSCT model.
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References

SHOWING 1-10 OF 66 REFERENCES
Decreased Levels of Circulating IL17-Producing CD161+CCR6+ T Cells Are Associated with Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation
TLDR
It is shown that functional CD161+CCR6+ co-expressing T cells disappear from the circulation and home to GVHD-affected tissue sites, which supports the hypothesis that CCR6+CD161-expressed T cells may be involved in the immune pathology of GV HD following their CCL20-dependent recruitment into affected tissues.
Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma.
TLDR
A logical explanation for the propensity of allogeneic stem cell transplantation to invoke sclerodermatous GVHD is provided and a therapeutic strategy for intervention is suggested.
SOCS3 regulates graft-versus-host disease.
TLDR
Surprisingly, SOCS3(-/Deltalck) donor T cells also induced severe, transforming growth factor beta- and IFNgamma-dependent, sclerodermatous GVHD, suggesting the delivery of small molecule SOCS 3 mimetics may prove to be useful for the inhibition of both acute and chronic GV HD.
Tc17 CD8 T Cells: Functional Plasticity and Subset Diversity1
TLDR
Adoptive transfer of highly purified, Ag-specific IL-17-secreting Tc17 cells into Ag-bearing hosts resulted in near complete conversion to an IFN-γ-Secreting phenotype and substantial pulmonary pathology, demonstrating functional plasticity.
A Th17‐like developmental process leads to CD8+ Tc17 cells with reduced cytotoxic activity
TLDR
The data point to the existence of mutually exclusive CTL and Tc17 developmental pathways in vitro and in vivo.
IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis.
TLDR
The results reveal that Tc17 cells contribute to the initiation of CNS autoimmunity in mice and humans by supporting Th17 cell pathogenicity.
Adoptive Transfer of Tumor-Specific Tc17 Effector T Cells Controls the Growth of B16 Melanoma in Mice
In vitro generated OVA-specific IL-17–producing CD8 T effector cells (Tc17) from OT-1 mice, adoptively transferred into B16-OVA tumor-bearing mice, controlled tumor growth in early and late stage…
Tc17, a Unique Subset of CD8 T Cells That Can Protect against Lethal Influenza Challenge1
TLDR
IL-17-secreting CD4 T (Th)17 and CD8 T (Tc)17 effector cells are found in the lung following primary challenge with influenza A and that blocking Ab to IL-17 increases weight loss and reduces survival, and protection afforded by Tc17 effectors is less perforin but more IFN-γ dependent.
Type 17 CD8+ T cells display enhanced antitumor immunity.
TLDR
Improved antitumor immunity was associated with increased expression of IL-7R-alpha, decreased expression of killer cell lectin-like receptor G1, and enhanced persistence of the transferred cells, and have implications for the improvement of CD8(+) T cell-based adoptive immunotherapy.
Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation.
TLDR
It is concluded that donor pretreatment with ProGP-1 is superior to G-CSF for the prevention of GVHD after allogeneic SCT, primarily due to incremental affects on T-cell phenotype and function.
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