Identifying Foxp3-Expressing Suppressor T Cells with a Bicistronic Reporter

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-04, Vol.102 (14), p.5126-5131
• Main Authors: Wan, Yisong Y., Flavell, Richard A.
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antibodies; Antigen presenting cells; B lymphocytes; Base Sequence; Biological Sciences; Bone marrow cells; Cellular immunity; Cytometry; DNA - genetics; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Forkhead Transcription Factors; Gene Expression; Genes, Reporter; Immune system; Immunology; 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; Red Fluorescent Protein; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Severe Combined Immunodeficiency - metabolism; T cell antigen receptors; T cell receptors; T lymphocytes; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Thymocytes; Transforming Growth Factor beta - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0501701102

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-β in activated CD4 T cells in vitro. Finally, we demonstrated that non-Foxp3-expressing CD4T 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.