Stability of the regulatory T cell lineage in vivo

By Y. Rubtsov, R. Niec, Steven Z. Josefowicz, Li Li, J. Darce, D. Mathis, C. Benoist, Alexander Y. Rudensky. Science, 2010

758 citations recorded by the source corpus.

Self-Renewing T Cells The homeostasis of cell populations within an organism can be achieved through a variety of mechanisms, including the differentiation of precursor populations, self-renewal of terminally differentiated cells, or by programming cells to be extremely long-lived. Regulatory T cells that express the transcription factor Foxp3 are critical for maintaining immune tolerance by preventing excessive inflammation and autoimmunity. Rubtsov et al. (p. 1667) now use genetic fate mapping and cell transfer studies in vivo to demonstrate that Foxp3-expressing cells are remarkably stable under both basal and inflammatory conditions. Thus, regulatory T cells appear to be maintained through self-renewal and should maintain their identity if used in adoptive cell therapies for treatment of autoimmunity or other inflammatory disorders. A subset of T cells that suppress immune-mediated inflammation is maintained by self-renewal. Tissue maintenance and homeostasis can be achieved through the replacement of dying cells by differentiating precursors or self-renewal of terminally differentiated cells or relies heavily on cellular longevity in poorly regenerating tissues. Regulatory T cells (Treg cells) represent an actively dividing cell population with critical function in suppression of lethal immune-mediated inflammation. The plasticity of Treg cells has been actively debated because it could factor importantly in protective immunity or autoimmunity. By using inducible labeling and tracking of Treg cell fate in vivo, or transfers of highly purified Treg cells, we have demonstrated notable stability of this cell population under physiologic and inflammatory conditions. Our results suggest that self-renewal of mature Treg cells serves as a major mechanism of maintenance of the Treg cell lineage in adult mice.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/27afc1276b278fa972e3a215d0440ccb9ba6921a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Oncology

Citations in the corpus

Molecular Mechanisms of Treg-Mediated T Cell Suppression (2012, background): “Plasticity between CD4 + T cell subsets might be higher than originally anticipated, although the stability of the Treg lineage in vivo is highly controversial (Zhou et al., 2009; Rubtsov et al., 2010).”
Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation (2011, positive): “To address this important caveat, we employed inducible ablation of the Il10rafl allele in Treg cells by using Cre-ERt2 recombinase and assessed Foxp3 expression (Rubtsov et al., 2010).”
The role of interleukin-2 during homeostasis and activation of the immune system (2012, background): “Thus, following acute ablation of IL-2 action by injection of a neutralizing IL-2-specific monoclonal antibody, the numbers of FOXP3 + T Reg cells decrease, and there is also a reduction of FOXP3 expression levels in these cell”
Extrathymically generated regulatory T cells control mucosal Th2 inflammation (2012, methodology): “Thus, we next employed genetic fate mapping using inducible Cre recombinase expressed in a T reg -specific manner ( Foxp3 EGFP-CRE-ERT2 ) and a Rosa26–YFP recombination reporter allele (R26Y”
Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. (2012, background): “The emerging notion of environment-induced Treg cell reprogramming has been actively debated but has remained highly controversial (Bailey-Bucktrout and Bluestone, 2011; Hori, 2011; Rubtsov et al., 2010).”
Development and maintenance of regulatory T cells. (2013, background): “Also, an in vivo cell-fate-chasing study has shown that Foxp3+ nTreg cells represent a stable cell lineage that is capable of sustaining Foxp3 expression and suppressive function overmultiple rounds of cell division, even in inflammatory environments (Rubtsov et al., 2010).”
Phenotypic and functional specialization of FOXP3+ regulatory T cells (2011, methodology): “However, using a similar reporter mouse system to monitor T Reg cell stability, Rudensky's group recently demonstrated that FOXP3 expression by T Reg cells is remarkably stable, even in highly inflammatory setting”
Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets (2011, background): “stable pool of important immune regulatory cells (18), and lipid oxidation may be central in contributing to their maintenance and self-renewal.”
The Balance of Th17 versus Treg Cells in Autoimmunity (2018, background): “In these mice, Foxp3+ cells hardly lost Foxp3 expression under both homeostatic and autoimmune inflammatory conditions, suggesting that Treg cells are highly stable [106].”
Regulatory T Cells and Human Disease. (2020, background): “In most circumstances Tregs display a high level of lineage stability, retaining their suppressive activity and FoxP3 expression despite various inflammatory stimuli (76).”
Regulatory T Cells: Mechanisms of Differentiation and Function (2012, background): “A bistable feed-forward autoregulatory loop could explain the remarkable stability of Foxp3 expression observed in mature Treg cells (179).”