Human CD4+CD25+ cells: A naturally occurring population of regulatory T cells

Wan Fai Ng, Phillip J. Duggan, Frederique Ponchel, Giuseppe Matarese, Giovanna Lombardi, A. David Edwards, John D. Isaacs, Robert I. Lechler

Research output: Contribution to journalArticle

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Abstract

Despite thymic deletion of cells with specificity for self-antigens, autoreactive T cells are readily detectable in the normal T-cell repertoire. In recent years, a population of CD4+ T cells that constitutively express the interleukin-2 receptor-α chain, CD25, has been shown to play a pivotal role in the maintenance of self-tolerance in rodent models. This study investigated whether such a regulatory population exists in humans. A population of CD4+CD25+ T cells, taken from the peripheral blood of healthy individuals and phenotypically distinct from recently activated CD4+ T cells, was characterized. These cells were hyporesponsive to conventional T-cell stimuli and capable of suppressing the responses of CD4+CD25- T cells in vitro. Addition of exogenous interleukin-2 abrogated the hyporesponsiveness and suppressive effects of CD4+CD25+ cells. Suppression required cell-to-cell contact but did not appear to be via the inhibition of antigen-presenting cells. In addition, there were marked changes in the expression of Notch pathway molecules and their downstream signaling products at the transcriptional level, specifically in CD4+CD25+ cells, suggesting that this family of molecules plays a role in the regulatory function of CD4+CD25+ cells. Cells with similar phenotype and function were detected in umbilical venous blood from healthy newborn infants. These results suggest that CD4+CD25+ cells represent a population of regulatory T cells that arise during fetal life. Comparison with rodent CD4+CD25+ cells suggests that this population may play a key role in the prevention of autoimmune diseases in humans.

Original languageEnglish
Pages (from-to)2736-2744
Number of pages9
JournalBlood
Volume98
Issue number9
DOIs
Publication statusPublished - Nov 1 2001

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T-cells
Regulatory T-Lymphocytes
T-Lymphocytes
Population
Blood
Rodentia
Molecules
Interleukin-2 Receptors
Autoantigens
Self Tolerance
Umbilicus
Interleukin-2
Antigen-Presenting Cells
Autoimmune Diseases
Newborn Infant
Phenotype

ASJC Scopus subject areas

  • Hematology

Cite this

Ng, W. F., Duggan, P. J., Ponchel, F., Matarese, G., Lombardi, G., David Edwards, A., ... Lechler, R. I. (2001). Human CD4+CD25+ cells: A naturally occurring population of regulatory T cells. Blood, 98(9), 2736-2744. https://doi.org/10.1182/blood.V98.9.2736

Human CD4+CD25+ cells : A naturally occurring population of regulatory T cells. / Ng, Wan Fai; Duggan, Phillip J.; Ponchel, Frederique; Matarese, Giuseppe; Lombardi, Giovanna; David Edwards, A.; Isaacs, John D.; Lechler, Robert I.

In: Blood, Vol. 98, No. 9, 01.11.2001, p. 2736-2744.

Research output: Contribution to journalArticle

Ng, WF, Duggan, PJ, Ponchel, F, Matarese, G, Lombardi, G, David Edwards, A, Isaacs, JD & Lechler, RI 2001, 'Human CD4+CD25+ cells: A naturally occurring population of regulatory T cells', Blood, vol. 98, no. 9, pp. 2736-2744. https://doi.org/10.1182/blood.V98.9.2736
Ng WF, Duggan PJ, Ponchel F, Matarese G, Lombardi G, David Edwards A et al. Human CD4+CD25+ cells: A naturally occurring population of regulatory T cells. Blood. 2001 Nov 1;98(9):2736-2744. https://doi.org/10.1182/blood.V98.9.2736
Ng, Wan Fai ; Duggan, Phillip J. ; Ponchel, Frederique ; Matarese, Giuseppe ; Lombardi, Giovanna ; David Edwards, A. ; Isaacs, John D. ; Lechler, Robert I. / Human CD4+CD25+ cells : A naturally occurring population of regulatory T cells. In: Blood. 2001 ; Vol. 98, No. 9. pp. 2736-2744.
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