Functional and genomic analyses of FOXP3-transduced Jurkat-T cells as regulatory T (Treg)-like cells.
FOXP3, a forkhead transcription factor is essential for the development and function of CD4(+)CD25(+) regulatory T cells (Tregs). In contrast to conversion of murine naive T cells to Tregs by transduction of Foxp3, it is controversial whether ectopic expression of FOXP3 in human CD4(+) T cells is sufficient for acquisition of suppressive activity. Here, we show that retroviral transduction of FOXP3 induces a Treg phenotype in human leukemic CD4(+) Jurkat-T cells, evidenced by increased expression of Treg-associated cell surface markers as well as inhibition of cytokine production. Furthermore, FOXP3-transduced Jurkat-T cells suppress the proliferation of human CD4(+)CD25(-) T cells. Additionally, DNA microarray analysis identifies Treg-related genes regulated by FOXP3. Our study demonstrates that enforced expression of FOXP3 confers Treg-like properties on Jurkat-T cells, which can be a convenient and efficient Treg-like cell model for further study to identify Treg cell surface markers and target genes regulated by FOXP3.
Kim
Joon-Young
JY
Cancer Stem Cell Section, Laboratory of Cancer Prevention, NCI-Frederick, 1050 Boyles Street, Building 560, Room 21-78, Frederick, MD 21702, USA. Electronic address: jykim@ncifcrf.gov.
Kim
Han-Jong
HJ
Cancer Stem Cell Section, Laboratory of Cancer Prevention, NCI-Frederick, 1050 Boyles Street, Building 560, Room 21-78, Frederick, MD 21702, USA.
Hurt
Elaine M
EM
Cancer Stem Cell Section, Laboratory of Cancer Prevention, NCI-Frederick, 1050 Boyles Street, Building 560, Room 21-78, Frederick, MD 21702, USA.
Chen
Xin
X
Basic Research Program, SAIC-Frederick, Inc., NCI-Frederick, MD 21702 USA.
Howard
O M Zack
OMZ
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Farrar
William L
WL
Cancer Stem Cell Section, Laboratory of Cancer Prevention, NCI-Frederick, 1050 Boyles Street, Building 560, Room 21-78, Frederick, MD 21702, USA. Electronic address: farrar@mail.ncifcrf.gov.
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D012190:Retroviridae / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014162:Transfection
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B