Transient regulatory T-cells: A state attained by all activated human T-cells

Vinodh Pillai, Sterling B. Ortega, C. K. Wang, Nitin J. Karandikar

Research output: Contribution to journalArticlepeer-review

302 Scopus citations


CD4+CD25+FOXP3+ regulatory T-cells (Tregs) form an important arm of the immune system responsible for suppressing untoward immune responses. Tregs can be thymically derived or peripherally induced, even from CD4+CD25-FOXP3- T-cells. FOXP3 expression and in vitro suppressive activity are considered unique hallmarks of this dedicated and stable lineage of regulatory cells. Here we show that virtually all human CD4+CD25-FOXP3- T-cells and CD8+CD25-FOXP3- T-cells attain a transient FOXP3+CD25+ state during activation. In this state of activation, these cells possess the classic phenotype of Tregs, in that they express similar markers and inhibit in vitro proliferation of autologous CD4+CD25- T-cells. This state is characterized by suppressed IFN-γ production and robust TNF-α and IL-10 production. Interestingly, the great majority of the activated cells eventually downregulate FOXP3 expression, with a concomitant drop in suppressive ability. Our results show that, in humans, FOXP3 expression and Treg functionality are not exclusive features of a stable or unique lineage of T-cells but may also be a transient state attained by almost all T-cells. These results warrant caution in interpreting human studies using FOXP3 and suppressive activity as readouts and suggest that attempts to induce "Tregs" may paradoxically result in induction of effector T-cells, unless stability is confirmed.

Original languageEnglish (US)
Pages (from-to)18-29
Number of pages12
JournalClinical Immunology
Issue number1
StatePublished - Apr 2007


  • CD4
  • CD8
  • FOXP3
  • Human
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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