title: Immune tolerance: are regulatory T cell subsets needed to explain suppression of autoimmunity?
abstract: The potential for self-reactive T cells to cause autoimmune disease is held in check by Foxp3(+)  regulatory T cells (Tregs), essential mediators of peripheral immunological tolerance. Tregs have the capacity to suppress multiple branches of the immune system, tightly controlling the different subsets of effector T cells across multiple different tissue environments. Recent genetic experiments have found mutations that disrupt specific Treg: effector T cell relationships, leading to the possibility that subsets of Tregs are required to suppress each subset of effector T cells. Here we review the environmental factors and mechanisms that allow Tregs to suppress specific subsets of effector T cells, and find that a parsimonious explanation of the genetic data can be made without invoking Treg subsets. Instead, Tregs show a functional and chemotactic plasticity based on microenvironmental influences that allows the common pool of cells to suppress multiple distinct immune responses.
authors.affiliation: VIB Autoimmune Genetics Laboratory, University of Leuven, Leuven, Belgium.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.forename: Stephanie
authors.initials: S
authors.lastname: Humblet-Baron
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
mesh_terms: D000818:Animals; D015551:Autoimmunity; D019070:Cell Lineage; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D051560:Proto-Oncogene Proteins c-bcl-6; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D000098815:T-bet Transcription Factor; D000099218:Interferon Regulatory Factor-4
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D050835:Interferon Regulatory Factors; D016753:Interleukin-10; D051560:Proto-Oncogene Proteins c-bcl-6; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C418974:FOXP3 protein, human