IL-7 Enhances Survival of Human CD56bright NK Cells

Abstract

Lymphoid differentiation and activation critically depend on cytokine stimulation and the interleukin-7 (IL-7) signaling in particular. Although it has been demonstrated that IL-7 may play a role in natural killer (NK) cell maturation, the effect of IL-7 stimulation on mature human NK cells has not been studied. We, therefore, investigated the expression and functional activity of IL-7Ralpha on mature NK populations from adult blood. In this article, we demonstrate that IL-7Ralpha is specifically expressed in the CD56bright noncytotoxic cytokine-producing NK subset. Importantly, this expression is thymus independent, contrary to what is observed in mice. In addition, we show that IL-7Ralpha is expressed at higher levels on NKG2A+CD56bright NK cells. In contrast to IL-15 stimulation, IL-7 does not increase NK cell cytotoxicity, interferon-gamma production, or the expression of activation markers, indicating that these cytokines play different functions in NK homeostasis and activation. However, IL-7 promotes the survival of the CD56bright NK subset and inhibits apoptosis by increasing BCL2 expression. These data should be taken into account when considering the clinical use of IL-7, particularly after stem cell transplantation.

Interleukin-7 expression and its effect on natural killer cells in patients with multiple sclerosis

“…1D). This finding is consistent with previous findings of down-regulation of IL-7R by IL-7 (Michaud et al, 2010b; Park et al, 2004), which suggests a specific regulator role of IL-7 on IL-7Rα.…”

“…The impact of IL-7/IL-7Rα signaling on CD4 + T cells (Kreft et al, 2012a), Treg cells (Haas et al, 2011), and CD8 + T cells (Kreft et al, 2012b) in MS has been reported to demonstrate that this pathway may subsequently enhance the pathogenicity of these immune cells. The importance of this pathway for NK cell homeostasis is underlined by several studies in both healthy human and animals (Lundstrom et al, 2012; Mazzucchelli and Durum, 2007; Michaud et al, 2010a); however, its impact on NK cell function in MS has not yet been reported.…”

Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the γc cytokines and TGF-β1

“…Freshly isolated NK cells express high amount of IL-2R␤ that can be used by both IL-2 and IL-15 (A.G.K., unpublished results, March 2011), 35 whereas the highly specific IL-15R␣ and IL-2R␣ chains appear predominantly on the surface of NK cells after stimulation (A.G.K., unpublished results, March 2011). 19,36 IL-7R␣ is expressed on the CD56 bright subset of NK cells, 50 and the cytokine receptor is expressed at lower level than that of IL-2 or IL-15 receptors (A.G.K., unpublished results, March 2011). Thus the differences we observe in the strength of the cytokine effect likely reflect the fact that there are different levels of the cytokine receptors expressed by NK cells.…”

Adoptive Cellular Therapy of Cancer: Exploring Innate and Adaptive Cellular Crosstalk to Improve Anti-Tumor Efficacy

“…Importantly, these T cells have been shown to differentiate into long-lived memory cells after acute antigen exposure [137,138]. It has been demonstrated that IL-7 also functions to enhance NK cell survival [139], although it appears this cytokine has no major role in the development of mature NK cells [140]. In addition, a recent study reports that human NKT cells are hyper-responsive in vitro to IL-7, leading to induced proliferation and increased frequency of cells expressing the terminal differentiation marker, CD161 [141].…”