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The functional characterization of interleukin-10 receptor expression on
human natural killer cells
WE Carson, MJ Lindemann, R Baiocchi, M Linett, JC Tan, CC Chou, S Narula and MA Caligiuri
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263,
USA.
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.
Volume 85,
Issue 12,
pp. 3577-3585,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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