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

Lookup NU author(s): Professor Fai NgORCiD, Professor John IsaacsORCiD


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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-alpha 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.

Publication metadata

Author(s): Isaacs JD; Ng WF; Duggan PJ; Ponchel F; Matarese G; Lombardi G; Edwards AD; Lechler RI

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2001

Volume: 98

Issue: 9

Pages: 2736-2744

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood.V98.9.2736


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