Stability of the Regulatory T Cell Lineage in Vivo

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.

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