title: Stimulation-dependent induction of CD154 on a subset of CD4+ FoxP3+ T-regulatory cells.
abstract: CD40-ligand/CD154 is predominantly expressed on activated CD4 T cells and plays a central role in regulating CD4 T-cell-dependent responses. To define the relative abilities of CD4 T-cell functional subsets in the induction of CD154--specifically FoxP3- effector, versus FoxP3+ regulatory, CD4 T cells--multiple CD4 T cell preparations were isolated from B6 and B6.FoxP3-GFP mice and stimulated in vitro to examine the kinetics of stimulation-dependent CD154 expression. CD154 was induced in 40-60% of total CD4 T cells in various cell preparations. However, despite similar kinetics of CD154-induced expression, the average percentage of CD154 expression among CD4+ FoxP3+ T regulatory (Treg) cells was only about 4-9%. Such differential, stimulation-dependent CD154 induction by total CD4+ T cells versus CD4+ FoxP3+ Treg cells was consistent, despite multiple stimulation conditions utilizing a variety of cell preparations of different composition. Similar induction of CD154 occurred irrespective of whether the CD4+ FoxP3+ Treg cells were first sorted to 98% purity and stimulated in vitro alone, or stimulated as non-purified cells in the presence of CD4+ FoxP3- T effector cells, suggesting that CD154 induction by CD4+ FoxP3+ Treg cells is regulated by cell-intrinsic mechanisms. Differential CD154 induction may be a key factor in determining the distinguishable functions of FoxP3- T-effector, versus FoxP3+ Treg, CD4+ T cells.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA. Wen.Li@Dartmouth.edu
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Carlson
authors.forename: William R
authors.initials: WR
authors.lastname: Green
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D023201:CD40 Ligand