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PMID: 15795373 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 14 ·2005-04-05 ·Pages 5126-31

Wan YY, Flavell RA

Abstract

Regulatory T cells are critical for maintaining self-tolerance and to negatively regulate immune responses. Foxp3 is a regulatory T cell-specific transcription factor that functions as the master regulator of the development and function of regulatory T cells. Here, we report the generation of a mouse model, in which a bicistronic reporter expressing a red fluorescent protein has been knocked into the endogenous Foxp3 locus. Using this mouse model, we assessed Foxp3 expression in various lymphocyte compartments and identified previously unreported Foxp3-expressing cells. In addition, we showed that de novo Foxp3 expression along with suppressive function were induced by TGF-beta in activated CD4 T cells in vitro. Finally, we demonstrated that non-Foxp3-expressing CD4 T cells could not be converted into Foxp3-expressing cells upon adoptive transfer into immunodeficient hosts. This Foxp3 bicistronic reporter knockin mouse model should greatly enhance the study of regulation and function of Foxp3-expressing regulatory T cells.

MeSH Terms
Adoptive Transfer Animals Base Sequence DNA/genetics DNA-Binding Proteins/deficiency,genetics,metabolism Forkhead Transcription Factors Gene Expression Genes, Reporter In Vitro Techniques Luminescent Proteins/genetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Models, Animal Models, Immunological Recombinant Proteins/genetics Severe Combined Immunodeficiency/genetics,immunology,metabolism T-Lymphocytes, Regulatory/drug effects,immunology,metabolism Transforming Growth Factor beta/pharmacology
Chemicals
DNA-Binding Proteins Forkhead Transcription Factors Foxp3 protein, mouse Luminescent Proteins Recombinant Proteins Transforming Growth Factor beta red fluorescent protein DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wan Yisong Y
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Flavell Richard A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0501701102
Published
2005-04-05
Epub
2005-00-28
Pages
5126-31
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC556008
Subset
IM
Grants
NIDDK NIH HHS · R01 DK051665 · United States
NIDDK NIH HHS · R01 DK51665 · United States
External Links
PubMed source DOI: 10.1073/pnas.0501701102 PMC Full Text View journal details
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