TOKITA Daisuke    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells.
Journal	Formal name：Journal of immunology (Baltimore, Md. : 1950) Abbreviation：J Immunol ISSN code：00221767/00221767
Domestic / Foregin	Foregin
Volume, Issue, Page	176(5),pp.2808-16
Author and coauthor	Raimondi Giorgio, Shufesky William J, Tokita Daisuke, Morelli Adrian E, Thomson Angus W
Publication date	2006/03
Summary	More effective discrimination between CD4+CD25+ regulatory T cells (Treg) and activated T cells would significantly improve the current level of purification of Treg and their therapeutic application. We observed that approximately 90% of Treg (positive for the nuclear transcription factor Forkhead winged helix protein-3 and able to inhibit naive T cell proliferation) isolated from the spleens or lymph nodes of normal mice did not express significant levels of the inhibitory receptor programmed cell death-1 (PD-1) on their surface, but retained PD-1 intracellularly. An identical phenotype was also identified for human CD4+CD25(high) T cells isolated from peripheral blood of healthy volunteers. By contrast, activated T cells expressed high levels of surface PD-1 that paralleled up-regulation of CD25 during effector cell expansion. This distinction allowed us to isolate CD4+CD25+PD-1(-) T cells with suppressive activity from mice immunized with mature allogeneic dendritic cells. Although purification was limited to resting Treg because TCR ligation induced up-regulation of surface PD-1, this strategy nevertheless represents a valuable step toward more definitive characterization of Treg and their improved purification for therapeutic assessment.
DOI	10.4049/jimmunol.176.5.2808
PMID	16493037