THE FUNCTIONAL-CHARACTERIZATION OF INTERLEUKIN-10 RECEPTOR EXPRESSIONON HUMAN NATURAL-KILLER-CELLS

Human natural killer (NK) cells are large granular lymphocytes that co nstitutively express functional forms of the interleukin-a receptor (I L-2R) and lyse tumor and virally infected cells without prior sensitiz ation. NK cells with high density expression of CD56 (CD56(bright)) ex press the high affinity IL-2R and proliferate in response to low (pico molar) concentrations of IL-2. CD56(dim) NK cells express the intermed iate affinity IL-2R and demonstrate enhanced cytotoxic activity withou t 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 hi ghly purified subsets of CD56(bright) and CD56(dim) NK cells. Binding studies using I-125-IL-10 indicated that resting human NK cells consti tutively express the IL-10 receptor protein at a surface density of ap proximately 90 receptor sites per cell, with a kd of similar to 1 nmol /L. Alone, IL-10 did not induce proliferation of CD56(bright) or CD56( dim) NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56( bright) NK cell subset mediated via the high-affinity IL-2R. In the ab sence of IL-2, IL-10 was able to induce significant NK cytotoxic activ ity against NK-resistant tumor cell targets in both subsets of NK cell s in a dose-dependent fashion. Furthermore, the combination of IL-10 a nd 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 necr osis factor-alpha, and granulocyte-macrophage colony-stimulating facto r 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 bindi ng directly to human NK cell subsets appear to be stimulatory and dose -dependent. In contrast to its direct effects on human T cells and mon ocytes/macrophages. IL-10 potentiates cytokine production by human NK cells. (C) 1995 by The American Society of Hematology.