Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 6, Pages 1621-1630Publisher
WILEY
DOI: 10.1002/eji.200737607
Keywords
cytokines; immune regulation; regulatory T cells; T cells
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Funding
- NCI NIH HHS [R44 CA124001-04, N01CO12400, N01 CO012400, R44 CA124001] Funding Source: Medline
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IL-15 is a member of they chain-dependent cytokines and known to affect innate and CD8(+) adaptive immune responses. Despite a growing interest in the use of IL-15 as an immunotherapeutic agent, the broad spectrum of immunoregulatory functions exerted by IL-15 has not been fully elucidated. Here, we demonstrate that IL-15 increases expression of CD25 and forkhead box transcription factor P3 (FOXP3), a master transcriptional regulator of regulatory T cells, in human peripheral CD4(+)CD25(-) T cells in the absence of antigenic stimulation. Comparisons involving IL-2 and IL-7 revealed that the induction of CD25(hi) and FOXP3 expression was most prominent with IL-15 and IL-2. More modest effects were seen with IL-7. Despite levels of FOXP3 expression comparable to that of conventional regulatory T cells, cytokine-induced CD4(+)CD25(hi)FOXP3(+) cells exerted only weak suppressor activity. Thus, the current study has demonstrated that IL-15 acts as a potent inducer of CD4(+)CD25(hi)FOXP3(+) cells in the periphery, and suggests a potential role for IL-15 in blunting immune activation. This study has provided further insights into the pleiotropic nature of IL-15 beyond the regulation of CD8(+) T cells.
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