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PMID: 18513999 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery.

Immunity ·Vol. 28 ·No. 6 ·2008-06-00 ·Pages 870-80

Ito T, Hanabuchi S, Wang YH, Park WR, Arima K, Bover L, Qin FX, Gilliet M, Liu YJ

Abstract

Previous studies suggest that thymus produces a homogenous population of natural regulatory T (Treg) cells that express a transcriptional factor FOXP3 and control autoimmunity through a cell-contact-dependent mechanism. We found two subsets of FOXP3+ natural Treg cells defined by the expression of the costimulatory molecule ICOS in the human thymus and periphery. Whereas the ICOS+FOXP3+ Treg cells used interleukin-10 to suppress dendritic cell function and transforming growth factor (TGF)-beta to suppress T cell function, the ICOS-FOXP3+ Treg cells used TGF-beta only. The survival and proliferation of the two subsets of Treg cells were differentially regulated by signaling through ICOS or CD28, respectively. We suggest that the selection of natural Treg cells in thymus is coupled with Treg cell differentiation into two subsets imprinted with different cytokine expression potentials and use both cell-contact-dependent and independent mechanisms for immunosuppression in periphery.

MeSH Terms
Antigens, Differentiation, T-Lymphocyte/immunology,metabolism CD28 Antigens/metabolism Cell Proliferation Cell Survival Cells, Cultured Dendritic Cells/immunology,metabolism Forkhead Transcription Factors/metabolism Humans Inducible T-Cell Co-Stimulator Protein Interleukin-10/immunology,metabolism Signal Transduction T-Lymphocyte Subsets/cytology,immunology,metabolism T-Lymphocytes, Regulatory/cytology,immunology,metabolism Thymus Gland/cytology,immunology,metabolism Transforming Growth Factor beta/immunology,metabolism
Chemicals
Antigens, Differentiation, T-Lymphocyte CD28 Antigens FOXP3 protein, human Forkhead Transcription Factors ICOS protein, human Inducible T-Cell Co-Stimulator Protein Transforming Growth Factor beta Interleukin-10
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ito Tomoki
Department of Immunology and Center of Cancer Immunology Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Hanabuchi Shino
Wang Yi-Hong
Park Woong Ryeon
Arima Kazuhiko
Bover Laura
Qin F Xiao-Feng
Gilliet Michel
Liu Yong-Jun
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2008.03.018
Published
2008-06-00
Epub
2008-00-29
Pages
870-80
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2709453
Subset
IM
Grants
NIAID NIH HHS · R01 AI062888 · United States
NIAID NIH HHS · R01 AI062888-05 · United States
NIAID NIH HHS · U19 AI071130 · United States
NIAID NIH HHS · U19 AI071130-01 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2008.03.018 PMC Full Text View journal details
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