IL-15 acts as a potent inducer of CD4+CD25high cells expressing forkhead box protein P3 (95.6)

Abstract

Abstract IL-15 is a member of the cytokine family that utilizes a common γ chain. While initially characterized as a T cell growth factor, predominantly involved in CD8+ T cell proliferation and survival, IL-15 is a pleiotropic cytokine that can affect both innate and adaptive immune responses. In the present study, we demonstrate that IL-15 increases expression of the alpha chain of the IL-2 receptor (CD25) and foxP3, a master control gene for the development and function of regulatory T cells, in human peripheral CD4+CD25− T cells without a need for additional antigenic stimulation signals. Side-by-side comparisons involving two other γc-cytokines: IL-2 and IL-7 revealed that the induction of CD25high and foxP3 expression was most prominent with IL-15 (median-fold increase: 46 and 53, respectively for CD25high and foxP3, p=0.0005) and IL-2 (32 and 42, p=0.0004). More modest effects were seen with IL-7 (18 and 12, p=0.0105). Despite levels of foxP3 expression comparable to that of conventional Tregs, these cytokine-induced CD4+CD25+foxP3+ cells exerted only weak suppressor activity. The current study has uncovered an unexpected function of IL-15 in the induction of CD4+CD25+foxP3+ cells from human peripheral T cells, thus helped to delineate and provided further insights into the pleiotropic nature of IL-15 beyond the regulation of CD8+ T cells. Funded in part by NCI Contract N01-CO-12400.