Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells

@article{Gagliani2013CoexpressionOC,
  title={Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells},
  author={Nicola Gagliani and Chiara Francesca Magnani and Samuel Huber and Monica Emma Gianolini and Mauro Pala and Paula Licona-Limon and Binggege Guo and De’Broski R. Herbert and Alessandro Bulfone and Filippo Trentini and Clelia Di Serio and Rosa Bacchetta and Marco Andreani and Leonie Brockmann and Silvia Gregori and Richard A. Flavell and Maria Grazia Roncarolo},
  journal={Nature Medicine},
  year={2013},
  volume={19},
  pages={739-746}
}
CD4+ type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers… Expand
Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages
TLDR
The data indicate that IL-10-producing Tr1 cells, Treg cells and CD8+ T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL- 10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa. Expand
Beyond type 1 regulatory T cells: co-expression of LAG3 and CD49b in IL-10-producing T cell lineages
TLDR
The data indicate that IL-10-producing Tr1 cells, Treg cells and CD8+ T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL- 10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa. Expand
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TLDR
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TLDR
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TLDR
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References

SHOWING 1-10 OF 57 REFERENCES
LAG-3 Expression Defines a Subset of CD4+CD25highFoxp3+ Regulatory T Cells That Are Expanded at Tumor Sites
TLDR
Ex vivo analysis showed that CD4+CD25highFoxp3+LAG-3+ T cells are functionally active cells that release the immunosuppressive cytokines IL-10 and TGF-β1, but not IL-2. Expand
Role of LAG-3 in regulatory T cells.
TLDR
It is proposed that LAG-3 marks regulatory T cell populations and contributes to their suppressor activity, which reduces their proliferative capacity and confers on them suppressionor activity toward effector T cells. Expand
A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis
TLDR
It is shown that chronic activation of both human and murine CD4+T cells in the presence of interleukin (IL)-10 gives rise to CD4-T-cell clones with low proliferative capacity, producing high levels ofIL-10, low levels of IL-2 and no IL-4. Expand
Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases.
TLDR
In vitro toxicity studies of human Tr1 cell product show a safety profile compatible with the use of these regulatory Tr1 lymphocytes for cell therapy, and characterization of the human cell therapy product shows an in vitro suppressive activity on T-cell proliferation dependent on the production of both IL-10 and TGF-beta. Expand
Negative Regulation of T Cell Homeostasis by Lymphocyte Activation Gene-3 (CD223)1
TLDR
It is shown that aged mice deficient in lymphocyte activation gene 3 (LAG-3), an MHC class II binding CD4 homologue, have twice as many T cells as wild-type controls and deregulation of T cell homeostasis by regulatory T cell-dependent and independent mechanisms is suggested. Expand
Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy
TLDR
An efficient and reproducible in vitro method to generate antigen-specific type 1 regulatory T-cell precursors starting from total peripheral blood cells with minimal cell manipulation and suitable for generating type 1 Regulatory T cells for regulatory T -cell-based therapies is developed. Expand
CD4+CD25−LAG3+ regulatory T cells controlled by the transcription factor Egr-2
TLDR
It is shown that IL-10-secreting Tregs can be delineated in normal mice as CD4+CD25−Foxp3− T cells that express lymphocyte activation gene 3 (LAG-3), an MHC-class-II-binding CD4 homolog. Expand
Identification and characterization of IL-10/IFN-γ–producing effector-like T cells with regulatory function in human blood
TLDR
To the authors' knowledge, this is the first report that identifies Tr1-like cells in human blood that have characteristics of chronically activated Th1 effector cells and are distinct from CD25+ T reg cells. Expand
Methods for in vitro generation of human type 1 regulatory T cells.
TLDR
This chapter outlines protocols to generate non-Ag- and Ag-specific Tr1 cell lines and assays used to characterize Tr1cell phenotype and functions and describes the rationale for selecting these protocols. Expand
IFN-α and IL-10 Induce the Differentiation of Human Type 1 T Regulatory Cells1
TLDR
It is demonstrated that IFN-α strongly enhances IL-10-induced differentiation of functional Tr1 cells, which represents a first major step in establishing specific culture conditions to generate T regulatory cells for biological and biochemical analysis, and for cellular therapy to induce peripheral tolerance in humans. Expand
...
1
2
3
4
5
...