title: Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor.
abstract: FoxP3 is a key transcription factor for the development and function of natural CD4(+) regulatory T cells (Treg cells). Here we show that human FoxP3(+)CD4(+) T cells were composed of three phenotypically and functionally distinct subpopulations: CD45RA(+)FoxP3(lo) resting Treg cells (rTreg cells) and CD45RA(-)FoxP3(hi) activated Treg cells (aTreg cells), both of which were suppressive in vitro, and cytokine-secreting CD45RA(-)FoxP3(lo) nonsuppressive T cells. The proportion of the three subpopulations differed between cord blood, aged individuals, and patients with immunological diseases. Terminally differentiated aTreg cells rapidly died whereas rTreg cells proliferated and converted into aTreg cells in vitro and in vivo. This was shown by the transfer of rTreg cells into NOD-scid-common gamma-chain-deficient mice and by TCR sequence-based T cell clonotype tracing in peripheral blood in a normal individual. Taken together, the dissection of FoxP3(+) cells into subsets enables one to analyze Treg cell differentiation dynamics and interactions in normal and disease states, and to control immune responses through manipulating particular FoxP3(+) subpopulations.
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyara
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kitoh
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shima
authors.forename: Kajsa
authors.initials: K
authors.lastname: Wing
authors.forename: Akira
authors.initials: A
authors.lastname: Niwa
authors.forename: Christophe
authors.initials: C
authors.lastname: Parizot
authors.forename: Cécile
authors.initials: C
authors.lastname: Taflin
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D017493:Leukocyte Common Antigens