Figure 2.

Anti-CD4 antibody-dependent natural killer (NK) cell activation. CD4⁺ T cells were cultured with purified anti-CD4 immunoglobulin G (IgG) from nonresponders or control antibodies and cocultured with NK cells at a ratio of 1:1. Intracellular CD107a and interferon γ (IFN-γ) expression in NK cells was analyzed by flow cytometry. A, Dot plots from a representative donor show CD107a and IFN-γ expression in NK cells in response to different concentrations of anti-CD4 antibodies from nonresponders. B, Percentages of NK cells expressing IFN-γ and CD107a in response to different concentrations of anti-CD4 IgG from 5 different nonresponders in vitro. Analyses were performed by the Friedman paired nonparametric test. C, Median percentages of NK cells expressing IFN-γ and CD107a in a mixed culture of CD4⁺ T cells and NK cells in the presence of anti-CD4 IgG from nonresponders, anti-CD4 IgG from nonresponders pretreated with sCD4 (control 1), anti-CD4 IgG–depleted total IgG from nonresponders (control 2), and zanolimumab (positive control) at 5 μg/mL in vitro. Analyses were performed using the Mann-Whitney U test (unpaired). D, Median percentages of NK cells expressing CD107a in healthy controls, responders, and nonresponders ex vivo. Analyses were performed using the Mann-Whitney U test (unpaired). FSC, forward scatter; SSC, side scatter.