IL‐15 acts as a potent inducer of CD4+CD25hi cells expressing FOXP3

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Abstract
IL‐15 is a member of the γ 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 CD25hi 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+CD25hiFOXP3+ cells exerted only weak suppressor activity. Thus, the current study has demonstrated that IL‐15 acts as a potent inducer of CD4+CD25hiFOXP3+ 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.Supporting Information for this article is available at www.wiley‐vch.de/contents/jc_2040/2008/37607_s.pdf