The functional characterization of interleukin-10 receptor expression on human natural killer cells

Abstract

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.

IL-10: A Multifunctional Cytokine in Viral Infections

“…NK and NKT cells are an essential effector arm of innate immunity that participates in the control of viral infections [42][43][44][45]. IL-10 has been shown to promote NK cell proliferation, cytokine production, and cytotoxicity in vitro [46][47][48][49][50], although in some in vivo settings it could modulate NK cell activity [51,52]. IL-10 acts as a prosurvival factor in activated NK cells by inhibiting activation-induced cell death [53].…”

Revisiting the Th1/Th2 Paradigm

“…Although originally described as cytokine synthesis inhibitory factor, IL-10 expresses proliferative, activating and chemotoactic properties upon various subsets of lymphocytes. In particular, IL-10 acts as a chemoattractant for CD8 þ T cells [47], and enhances the differentiation, growth and cytotoxic activity of CD8 þ cytotoxic T lymphocytes [48] and NK cells [49,50]. IL-10 extends the viability of mouse mast cell lines in vitro and synergizes with IL-3 and IL-4 to stimulate their proliferation.…”

cDNA cloning, genomic structure, molecular characterization and mRNA expression analysis of the Pekin duck interleukin‐10 receptor 1

“…IL-10 receptor 1 is expressed on most immune cells, and very low expression levels have been observed on a variety of nonhaematopoietic cells (Tan et al, 1993;Liu et al, 1994;Bourreille et al, 1999;Roth & Fisher, 1999;Moore et al, 2001). Differential expression of IL-10R1 plays an important role in IL-10-mediated immune regulation, and activation of certain immune cells such as monocytes and neutrophils increases mRNA expression, whereas expression levels have been shown to decrease following stimulation of T cells, B cells and NK cells (Carson et al, 1995;Jurlander et al, 1997;Denning et al, 2000;Crepaldi et al, 2001;Ding et al, 2001;Nagalakshmi et al, 2004). We observed most abundant expression of duIL-10R1 transcripts in spleen, thymus, PBMCs and lung and lower levels in bursa, cecal tonsil, cloacae, liver and kidney, while expression levels were unde- .…”

“…IL-10R1 is expressed on most haematopoietic cells, and differential expression plays an important role in IL-10-mediated immune regulation Jung et al, 2004). Activation of certain immune cells such as monocytes and neutrophils increases mRNA expression, whereas expression levels have been shown to decrease following stimulation of T cells, B cells and NK cells (Carson et al, 1995;Jurlander et al, 1997;Denning et al, 2000;Crepaldi et al, 2001;Ding et al, 2001;Nagalakshmi et al, 2004). IL-10R1 expression can be induced on nonhaematopoietic cells such as fibroblasts, and constitutive expression has been described on a variety of other cells such as colonic epithelium and placental cytotrophoblasts (Tan et al, 1993;Liu et al, 1994;Bourreille et al, 1999;Roth & Fisher, 1999;Moore et al, 2001).…”