Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells

Giorgio Raimondi, William J. Shufesky, Daisuke Tokita, Adrian E. Morelli, Angus W. Thomson

Research output: Contribution to journalArticlepeer-review


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 ∼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+CD25high 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.

Original languageEnglish (US)
Pages (from-to)2808-2816
Number of pages9
JournalJournal of Immunology
Issue number5
StatePublished - Mar 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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