title: Developmental plasticity of murine and human Foxp3(+) regulatory T cells.
abstract: Murine and human CD4(+) regulatory T (Treg) cells expressing the Forkhead box p3 (Foxp3) transcription factor represent a distinct, highly differentiated CD4(+) T cell lineage that is programmed for dominant self-tolerance and control of immune responses against a variety of foreign antigens. Sustained Foxp3 expression in these cells drives the differentiation of a regulatory phenotype and ensures the stability of their suppressive functions under a variety of inflammatory settings. Some recent studies have challenged this premise and advanced the notion that Foxp3(+) Treg cells manifest a high degree of functional plasticity that enables them to adapt and reprogram into effector-like T cells in response to various inflammatory stimuli. The concept of Treg cell plasticity remains highly contentious, with a high degree of variation in measured plasticity potential observed under different experimental conditions. In this chapter, we propose a unifying model of Treg cell plasticity, which hypothesizes that the stable fates of regulatory and effector T (Teff) cell lineages allow transient plasticity into the alternative lineage under a discrete set of microenvironmental influences associated with, respectively, the initiation and resolution phases of infection. This model utilizes a theoretical framework consistent with the requirements for effective immune regulation and accounts for both the extraordinary long-term stability of Treg cells and the observed fate plasticity.
authors.affiliation: Autoimmune Genetics Laboratory, VIB and University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.forename: Ciriaco A
authors.initials: CA
authors.lastname: Piccirillo
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007239:Infections / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit
keywords: Differentiation; Epigenetics; Foxp3; Infection; Plasticity; Tolerance; Treg