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

Vinodh PILLAI; Sterling B ORTEGA; C. K WANG; Nitin J KARANDIKAR

doi:10.1016/j.clim.2006.10.014

Back

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

Journal article

Open access

Peer reviewed

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

Vinodh PILLAI, Sterling B ORTEGA, C. K WANG and Nitin J KARANDIKAR

Clinical immunology (Orlando, Fla.), Vol.123(1), pp.18-29

2007

DOI: 10.1016/j.clim.2006.10.014

PMCID: PMC1868523

PMID: 17185041

Files and links (1)

url

https://doi.org/10.1016/j.clim.2006.10.014View

Published (Version of record) Open Access

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.

Immunopathology

Fundamental and applied biological sciences. Psychology

Fundamental immunology

Biological and medical sciences

Medical sciences

Details

Title: Subtitle: Transient regulatory T-cells : A state attained by all activated human T-cells
Creators: Vinodh PILLAI - Department of Pathology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-9072, United States
Sterling B ORTEGA - Department of Pathology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-9072, United States
C. K WANG - Department of Pathology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-9072, United States
Nitin J KARANDIKAR - Department of Pathology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-9072, United States
Resource Type: Journal article
Publication Details: Clinical immunology (Orlando, Fla.), Vol.123(1), pp.18-29
DOI: 10.1016/j.clim.2006.10.014
PMID: 17185041
PMCID: PMC1868523
NLM abbreviation: Clin Immunol
ISSN: 1521-6616
eISSN: 1521-7035
Publisher: Elsevier; San Diego, CA
Language: English
Date published: 2007
Academic Unit: Pathology
Record Identifier: 9984046832302771

Metrics

11 Record Views

291 Times Cited - Web of Science

See more details