Differentiation, phenotype, and function of interleukin-17-producing human Vγ9Vδ2 T cells.

  title={Differentiation, phenotype, and function of interleukin-17-producing human V$\gamma$9V$\delta$2 T cells.},
  author={Nadia Caccamo and Carmela La Mendola and Valentina Orlando and Serena Meraviglia and Matilde Todaro and Giorgio Stassi and Guido Sireci and Jean-Jacques Fourni{\'e} and Francesco Dieli},
  volume={118 1},
In healthy adults, the major peripheral blood γδ T-cell subset expresses the Vγ9Vδ2 TCR and displays pleiotropic features. Here we report that coculture of naive Vγ9Vδ2 T cells with phosphoantigens and a cocktail of cytokines (IL-1-β, TGF-β, IL-6, and IL-23), leads to selective expression of the transcription factor RORγt and polarization toward IL-17 production. IL-17(+) Vγ9Vδ2 T cells express the chemokine receptor CCR6 and produce IL-17 but neither IL-22 nor IFN-γ; they have a predominant… 

Figures from this paper

IL-21 Regulates the Differentiation of a Human γδ T Cell Subset Equipped with B Cell Helper Activity

A subset of human Vγ9Vδ2 lymphocytes, which, upon interaction with IL-21-producing CD4 TFH cells and B cells in secondary lymphoid organs, is implicated in the production of high affinity antibodies against microbial pathogens.

IL-2 Shapes the Survival and Plasticity of IL-17–Producing γδ T Cells

IL-2 can augment the γδT-17 response in favor of short-lived effectors with limited plasticity, particularly in the presence of IL-1β and IL-23, and may act to curtail the innate-like response of γ Greek T cells upon arrival of IL–2–producing adaptive immune cells at the site of inflammation.

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

The data reveal that the peripheral pool of γδ T cells retains a considerable degree of plasticity because it harbors “naive” precursors, which can be induced to produce IL-17 and replenish peripheral niches that are usually occupied by thymus-derived �γδT17 cells.

Interleukin 7 (IL-7) selectively promotes mouse and human IL-17–producing γδ cells

IL-17–producing CD27− γδ cells (γδ27− cells) are widely viewed as innate immune cells that make critical contributions to host protection and autoimmunity. However, factors that promote them over

CD3bright signals on γδ T cells identify IL‐17A‐producing Vγ6Vδ1+ T cells

A new way to specifically analyze IL‐17‐producing Vγ6/Vδ1+ T cells based on the level of CD3 signals is proposed, which reinforces the crucial role of this γδ T‐cell subset in respiratory and skin disorders.

IL-17–Producing Vγ4+ γδ T Cells Require Sphingosine 1-Phosphate Receptor 1 for Their Egress from the Lymph Nodes under Homeostatic and Inflammatory Conditions

It is suggested that inhibition of S1P1-dependent egress of pathogenic IL-17–producing Vγ4+ γδ T cells from the DLN may partly contribute the clinical therapeutic effects of FTY720 in relapsing multiple sclerosis.

IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+Vγ6+γδ T cells

It is shown that during autoimmune arthritis development αβ CD4+T cells recruit a subset of IL-17-producing γδ T cells to the joints, and that both components are essential to cause pathology in a mouse model of the disease.

Human γδ Thymocytes Are Functionally Immature and Differentiate into Cytotoxic Type 1 Effector T Cells upon IL-2/IL-15 Signaling

It is found that ex vivo–isolated γδ thymocytes produced negligible IFN-γ and lacked cytolytic activity against leukemia cells, and TCR activation was dispensable for these stages of functional differentiation.

IL-17+ γδ T cells as kick-starters of inflammation

The current knowledge of the development, activation and pathophysiological functions of γδ17 T cells is reviewed, aiming to increase the awareness in the community of the therapeutic potential of this 'other side' of IL-17-mediated immune responses.

Development and function of interleukin 17–producing γδ T cells

The role of γδT17 cells in animal models of autoimmunity will be discussed as well as the prerequisites for the development of human γ Greek T cells and their potential importance for human disease conditions.



Cytokine Requirements for the Differentiation and Expansion of IL-17A– and IL-22–Producing Human Vγ2Vδ2 T Cells

The data suggest that, like Th17 αβ T cells, Vγ2Vδ2 T cells can be polarized into Tγδ17 and T γδ1/17 populations with distinct cytokine requirements for their initial polarization and later maintenance.

Phenotypic and functional features of human Th17 cells

The demonstration of selective markers for human Th17 cells may help to understand their pathogenic role, and the identification of a subset of cells sharing features of both Th1 and Th17 may raise new issues concerning developmental and/or functional relationships between Th17 and Th1.

IL-17 and Th17 Cells.

The investigation of the differentiation, effector function, and regulation of Th17 cells has opened up a new framework for understanding T cell differentiation and now appreciate the importance of Th 17 cells in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.

Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells.

It is reported here that for human naive CD4(+) T cells, RORgammat expression and T(H)-17 polarization were induced by IL-1beta and enhanced byIL-6 but were suppressed by transforming growth factor-beta and IL-12.

Identification of CD25+ γδ T Cells As Fetal Thymus-Derived Naturally Occurring IL-17 Producers1

It was revealed that the fetal thymus-derived Vγ6+Vδ1+ T cells functionally differentiate to produce IL-17 within thymu and thereafter express CD25 to be maintained in the periphery.

CD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17–producing γδ T cell subsets

The cytokine profiles of peripheral γδ T cells are predetermined mainly by a mechanism involving CD27, and these phenotypes were established during thymic development.

Distinct Cytokine-Driven Responses of Activated Blood γδ T Cells: Insights into Unconventional T Cell Pleiotropy1

Broad plasticity emphasizes the capacity of γδ T cells to influence the nature of the immune response to different challenges and has implications for the ongoing clinical application of cytokines together with Vγ9/Vδ2 TCR agonists.

CD161 is a marker of all human IL‐17‐producing T‐cell subsets and is induced by RORC

Evidence is provided that umbilical cord blood naïve CD4+CD161− T cells, upon lentivirus‐mediated transduction with RORC2 can acquire the ability to express IL‐23R, IL‐1RI, and CD161, as well as to produce IL‐17.