title: Identification of an immediate Foxp3(-) precursor to Foxp3(+) regulatory T cells in peripheral lymphoid organs of nonmanipulated mice.
abstract: CD4(+)CD25(+) regulatory T cells (T reg cells) expressing the transcription factor Foxp3 can be induced from peripheral T cell receptor (TCR) transgenic CD4(+)CD25(-)Foxp3(-) T cells stimulated with noninflammatory dendritic cells presenting low amounts of agonist cognate antigen. However, limited evidence exists for extra-thymic T reg cell generation from non-TCR transgenic T cells in unmanipulated mice. We compared events early during agonist-driven generation of Foxp3(+) TCR transgenic T cells to polyclonal CD4(+) T cell populations in unmanipulated mice. We identified an interleukin-2- and phosphatidylinositol-3-kinase-dependent precommitted Foxp3(-) precursor to Foxp3(+) T reg cells in peripheral lymphoid organs. Transforming growth factor beta signaling played a minor role in the generation and subsequent differentiation of these T reg precursor cells.
authors.affiliation: Immunotolerance in Regeneration, Center for Regenerative Therapies Dresden, 01307 Dresden, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Schallenberg
authors.forename: Pei-Yun
authors.initials: PY
authors.lastname: Tsai
authors.forename: Julia
authors.initials: J
authors.lastname: Riewaldt
authors.forename: Karsten
authors.initials: K
authors.lastname: Kretschmer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008208:Lymphatic System / Q000166:cytology* / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D019041:L-Selectin; D037181:Lectins, C-Type; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens; C498833:Foxp3 protein, mouse