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Constitutive expression of high affinity interleukin 2 receptors on human CD16-natural killer cells in vivo
A Nagler1, L L Lanier, J H Phillips
1Becton Dickinson Monoclonal Center, Inc., San Jose, California 95131.
Insights
Human Natural Killer (NK) cells show differential responses to Interleukin-2 (IL-2) due to varying IL-2 receptor affinities. CD16- NK cells, with high and intermediate affinity receptors, are more responsive than CD16+ NK cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human Natural Killer (NK) cells are crucial immune cells with distinct subsets.
- NK cell function is modulated by Fc receptors (CD16) and Interleukin-2 (IL-2) receptors.
Purpose of the Study:
- To investigate the differential responsiveness of CD16- and CD16+ NK cells to IL-2.
- To characterize the IL-2 receptor expression and affinity on these NK cell subsets.
Main Methods:
- Phenotypic analysis of NK cell subsets (CD16+ vs. CD16-).
- Assessment of IL-2 receptor expression (p55 and p75) on NK cells.
- Scatchard analysis to determine IL-2 receptor binding affinity and number.
Main Results:
- CD16- NK cells co-express both p75 and p55 IL-2 receptors, while CD16+ NK cells express only p75.
- CD16- NK cells exhibit higher affinity IL-2 receptors (high and intermediate) compared to CD16+ NK cells (intermediate affinity only).
- CD16- NK cells show preferential proliferation and cytolytic activation in response to low IL-2 concentrations.
Conclusions:
- Differential IL-2 responsiveness in human NK cell subsets is mediated by distinct IL-2 receptor affinities.
- The presence of high-affinity IL-2 receptors on CD16- NK cells explains their enhanced sensitivity to IL-2.
Abstract:
The majority of human NK cells express low affinity IgG Fc receptors (CD16+), whereas a minor subset of NK cells lack Fc receptor expression (CD16-). In contrast to CD16+ NK cells that express only p75 IL-2 receptors, CD16- NK cells constitutively co-express both p75 and p55 IL-2 receptors in vivo and preferentially respond to low concentrations of IL-2 with increased cytolytic activation and proliferation. Scatchard analysis demonstrated the presence of approximately 1,200 high affinity (approximately 25 pM kD) and approximately 9,600 intermediate affinity (approximately 2 nM kD) IL-2 receptors on CD16- NK cells. CD16+ NK cells expressed only a single intermediate affinity IL-2 receptor of approximately 1.9 nM kD (approximately 9,000 sites per cell). The IL-2 binding data thus substantiated the phenotypic and functional studies and definitively show that the differential responsiveness of CD16- and CD16+ NK cells to IL-2 is manifested through different affinity IL-2 receptors.