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 journalArticle

275 Citations (Scopus)

Abstract

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
Volume123
Issue number1
DOIs
StatePublished - Apr 2007

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Regulatory T-Lymphocytes
T-Lymphocytes
Interleukin-10
Immune System
Down-Regulation
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Transient regulatory T-cells : A state attained by all activated human T-cells. / Pillai, Vinodh; Ortega, Sterling B.; Wang, C. K.; Karandikar, Nitin J.

In: Clinical Immunology, Vol. 123, No. 1, 04.2007, p. 18-29.

Research output: Contribution to journalArticle

Pillai, Vinodh ; Ortega, Sterling B. ; Wang, C. K. ; Karandikar, Nitin J. / Transient regulatory T-cells : A state attained by all activated human T-cells. In: Clinical Immunology. 2007 ; Vol. 123, No. 1. pp. 18-29.
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