Fig. 2: TCB-triggered immunological activation cascades of CD45RO+ CD4+ and GzmB+ CD8+ immune subsets yield mechanistic insight into the TCB mode of action. | Nature Biomedical Engineering

Fig. 2: TCB-triggered immunological activation cascades of CD45RO+ CD4+ and GzmB+ CD8+ immune subsets yield mechanistic insight into the TCB mode of action.

From: Analysis of off-tumour toxicities of T-cell-engaging bispecific antibodies via donor-matched intestinal organoids and tumouroids

Fig. 2

The figure follows the CD45RO+ CD4+ and GzmB+ CD8+ T-cell fractions over the treatment period (hereafter abbreviated as ‘both subsets’). The figure displays data for both subsets, following the immunological cascade and cytokine release at 10 µg ml−1 across the entire treatment duration (left panels) and at three different concentrations (0.1–10 µg ml−1) (right panels) of the indicated TCB at specific timepoints (denoted by asterisks). a, TCR (CD3) MFI highlights TCR internalization upon TCB stimulus in both subsets. b–d, Brefeldin A and Monensin were used to trap cytokines secreted in individual cells. Here we detected pro-inflammatory cytokine release by means of TNFɑ (b) and IFNγ (c) in both subsets, followed by GzmB exocytosis (d). e, Proliferative state of CD45RO+ CD4+ and Ki67+ GzmB+ CD8+ by Ki67+ antibody staining reiterates potent activation of immune cells. f, Concatenated contour plot of GzmB+ intracellular expression in both T-cell subsets 48 h post treatment, in which each columnar cloud represents the individual condition indicated. a–f, n = 2. g, Heat map of multiplex cytokine analysis performed on supernatants from treated wells across all timepoints and TCBs administered. Normalized per cytokine, mean per condition plotted (n = 3).

Source data

Back to article page