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Interleukin‐10‐secreting type 1 regulatory T cells in rodents and humans
- Maria Grazia Roncarolo, S. Gregori, M. Battaglia, R. Bacchetta, K. Fleischhauer, M. Levings
- BiologyImmunological Reviews
- 1 August 2006
Results from clinical protocols using Tr1 cells to modulate immune responses in vivo in autoimmunity, transplantation, and chronic inflammatory diseases will undoubtedly prove the biological relevance of these cells in immunotolerance.
Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells
The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr 1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation.
Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells.
- M. Levings, S. Gregori, E. Tresoldi, S. Cazzaniga, C. Bonini, M. Roncarolo
- 1 February 2005
A standardized and highly reproducible protocol to differentiate Tr cells by repetitive exposure of naive peripheral blood CD4(+) T cells to allogeneic iDCs is developed and can be used to generate large numbers of alloantigen-specific Tr1 cells for clinical use as a cellular therapy to restore peripheral tolerance.
Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway.
The data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells.
Tr1 cells: from discovery to their clinical application.
CD4+ regulatory T cells: mechanisms of induction and effector function.
Tr1 cells and the counter-regulation of immunity: natural mechanisms and therapeutic applications.
- M. Roncarolo, S. Gregori, R. Bacchetta, M. Battaglia
- Biology, MedicineCurrent topics in microbiology and immunology
The role of Tr1 cells in infectious diseases, autoimmunity, and transplant rejection in different pre-clinical disease models and in patients is addressed and the pathological settings in which Tr 1 cells can be beneficial to prevent or to cure the disease are highlighted.
Activation of the aryl hydrocarbon receptor promotes allograft-specific tolerance through direct and dendritic cell-mediated effects on regulatory T cells.
Oral administration of a water-soluble derivative of VAF347 (VAG539) promotes long-term graft acceptance and active tolerance in Balb/c mice that receive a transplant of MHC-mismatched pancreatic islet allografts.
The Cellular and Molecular Mechanisms of Immuno-Suppression by Human Type 1 Regulatory T Cells
The well known and newly discovered regulatory properties of human Tr1 cells are outlined and an in-depth comparison of the known suppressor mechanisms of Tr 1 cells with FOXP3+ Treg is provided.
Immunological Outcome in Haploidentical-HSC Transplanted Patients Treated with IL-10-Anergized Donor T Cells
This study provides the first indication of the feasibility of Tr1 cell-based therapy and paves way for the use of these Tr1 cells as adjuvant treatment for malignancies and immune-mediated disorders.