title: Human adipose-derived stromal/stem cells induce functional CD4+CD25+FoxP3+CD127- regulatory T cells under low oxygen culture conditions.
abstract: Human adipose tissue stromal/stem cells (ASCs) are known to induce proliferation of resting T cells under ambient (21%) O2 conditions; however, ASCs exist physiologically under lower oxygen (5% O2) conditions in adipose tissue. The effects of low oxygen levels on ASC immunomodulation of T cells are unknown. In this study, we show that ASCs stimulated proliferation of naive CD4(+) T cells and the percentage of CD25(+) T cells was significantly increased under both low and ambient O2. Forkhead box P3 (FoxP3) and transforming growth factor beta (TGF-β) mRNA expression were significantly increased when ASCs were cocultured with CD4(+) T cells under low compared with ambient O2 conditions. The low O2-induced regulatory T cells (iTregs) exhibited functionality when added to mixed lymphocyte reactions as demonstrated by inhibition of peripheral blood mononuclear cell proliferation, and by >300-fold increase in FoxP3 mRNA, and >2-fold increase in TGF-β mRNA expression. These results demonstrate that under physiologically relevant low O2 conditions, direct contact of human ASCs with naive CD4(+) T cells induced functional iTregs.
authors.affiliation: 1 Department of Structural and Cellular Biology, Tulane University , New Orleans, Louisiana.
authors.forename: Trivia P
authors.initials: TP
authors.lastname: Frazier
authors.forename: James B
authors.initials: JB
authors.lastname: McLachlan
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Tucker
authors.forename: Brian G
authors.initials: BG
authors.lastname: Rowan
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000328:Adult; D015704:CD4 Antigens / Q000276:immunology; D015687:Cell Hypoxia / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit