Fig. 2: CD155hi macrophages suppress anti-viral T cell responses.
a–c, Monocyte-derived Mϕ were generated from patients and controls. Gene expression signature for 14 immune checkpoint genes in healthy and CAD Mϕ (n = 6). qPCR results are shown as a heat map (a). Flow cytometry of CD155 surface expression in healthy and CAD Mϕ. Representative histograms and summary data from n = 27 controls and n = 27 patients are shown (b). Confocal immunofluorescence of CD155 protein expression in healthy and CAD Mϕ. Representative images from three independent experiments (c). d, Fluorescence microscopy of atherosclerotic plaque tissue sections stained for CD68 (green) and CD155 (red). Representative images from four experiments. e, Correlation of antigen-induced IFN-γ release and Mϕ CD155 expression in n = 34 patients with CAD. f,g, IFN-γ secretion after SARS-CoV-2 antigen (f, n = 10) or EBV antigen (g, n = 5) stimulation in the absence or presence of anti-CD155 antibodies. h,i, Frequencies of CD69+CD40L+ T cells induced by SARS-CoV-2 antigen (h, n = 8) or EBV antigen (i, n = 5) stimulation with and without CD155 blockade. j–m, Mϕ were transfected with control or CD155 siRNA before antigen loading. IFN-γ induction after stimulation with SARS-CoV-2 antigen (j, n = 10) or EBV antigen (k, n = 5). Frequencies of SARS-CoV-2-reactive CD69+ CD40L+ T cells (l, n = 6) and EBV-reactive CD69+CD40L+ T cells (m, n = 5). n, In vivo anti-SARS-CoV-2 T cell responses were measured in immunodeficient NSG mice that were reconstituted with human PBMCs and immunized with viral protein. Mϕ were transfected with control or CD155 siRNA before the adoptive transfer. After 1 week, antigen-induced human CD4+CD38+ T cells were measured in the spleen. Representative dot blots of CD4+CD38+ T cells and frequencies of CD4+CD38+ T cells. Data are from five experiments. Data are mean ± s.e.m. Comparison by one-way ANOVA. Correlation analysis with linear regression. P values are shown in each panel. CON, control; FMO, Fluorescence Minus One; MFI, mean fluorescence intensity.
