Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor.

Abstract

SummaryInterleukin 15 (IL-15) is a novel cytokine that has recently been doned and expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct popttlations of highly purified human natural killer (NK) cells. The CD56 b~ht subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R~ (p75), but not by anti-IL-2Rc~ (p55). The proliferative effects of IL-2 on CD56bns ht NK cells could be inhibited by both antibodies. CD56 ~n NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56 a~ NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibodydependent cdlular cytotoxicity, and NK cell production of interferon % tumor necrosis factor c~, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-21L8 monoclonal antibody. The binding of radiolabded IL-2 and IL-15 to CD56 d~n NK cells was inhibited in the presence of anti-IL-21LB. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK-enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function.

CD56bright NK cells after hematopoietic stem cell transplantation are activated mature NK cells that expand in patients with low numbers of T cells

“…Preferential activation and expansion of CD56 bright could have occurred in response to high cytokine levels in patients after HSCT [27][28][29] because CD56 bright proliferate much more vigorously when stimulated by IL-2 or IL-15 than CD56 dim [3,4,21,36]. To study whether ptCD56 bright had attributes of cytokine-activated CD56 bright , we compared the expression of CD27, CCR7, CD94, HLA-DR and perforin as well as the capacity to produce IFN-g of ptCD56 bright , of CD56 bright and of purified CD56 bright that were cultured for 6 days with IL-15 (NK ).…”

Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal

“…We monitored cytotoxicity with redirected lysis rather than with antigenic target cells and thus detected multiclonal activation by both cytokines. It is known that IL-2 or IL-15 will activate NK cells without receptor stimulation [5,6]. IL-15 without antigen(s) activates cytotoxic capacity of human T cells with a memoryassociated phenotype and may also activate naïve human CD8 + T cells [7,8].…”

Differential Role for IL‐2 and IL‐15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes

“…Both cytokines are therefore mutually exclusive in their production in various cell types [34]. Even though their amino acid sequence shows no homology [34,36], the biological action of both proteins seems to be similar as activators of CD4 + and CD8 + T lymphocytes, gd T cells, NK cells and B lymphocytes [40][41][42][43][44][45][46]. This could be explained by the observation that both IL-2 and IL-15 bind to the IL-2R b-and g cchain [34,36].…”