title: IL-17- and IFN-γ-secreting Foxp3+ T cells infiltrate the target tissue in experimental autoimmunity.
abstract: CD4(+)Foxp3(+) regulatory T cells (Tregs) have been considered crucial in controlling immune system homeostasis, and their derangement is often associated to autoimmunity. Tregs identification is, however, difficult because most markers, including CD25 and Foxp3, are shared by recently activated T cells. We show in this paper that CD4(+)Foxp3(+) T cells are generated in peripheral lymphoid organs on immunization and readily accumulate in the target organ of an autoimmune reaction, together with classical inflammatory cells, constituting up to 50% of infiltrating CD4(+) T cells. Most CD4(+)Foxp3(+) T cells are, however, CD25(-) and express proinflammatory cytokines such as IL-17 and IFN-γ, questioning their suppressive nature. Moreover, in vitro CD4(+) T lymphocytes from naive and autoimmune mice, stimulated to differentiate into Th1, Th2, Th17, and induced Tregs, display early mixed expression of lineage-specific markers. These results clearly point to an unprecedented plasticity of naive CD4(+) T cells, that integrating inflammatory signals may change their fate from the initial lineage commitment to a different functional phenotype.
authors.affiliation: Clinical Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Esposito
authors.forename: Francesca
authors.initials: F
authors.lastname: Ruffini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bergami
authors.forename: Livia
authors.initials: L
authors.lastname: Garzetti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Borsellino
authors.forename: Luca
authors.initials: L
authors.lastname: Battistini
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D007371:Interferon-gamma