A MALT1 inhibitor suppresses human myeloid DC, effector T-cell and B-cell responses and retains Th1/regulatory T-cell homeostasis
Fig 5
Effect of allosteric MALT1 inhibitors on activation, proliferation and cytokine production of human memory CD4+ CD45RO+ T cells.
(A) Representative FACS plots showing IFN-ɣ expression and cell trace violet (CTV) dilution in human memory CD4+ CD45RO+ T cells co-cultured with autologous monocytes and LPS and stimulated with anti-CD3 + anti-CD28 antibodies for 5 days in the absence or presence of 10 μM Compound 2, 5 μM mepazine or 100 μM z-VRPR-fmk. (B) Quantification of the percentage of cells expressing CD25 (top graph) and cells that have divided as defined by CTV dilution (lower graph), (C) and quantification of cells producing either IFN-ɣ, IL-17A, both IFN-ɣ+IL-17A or IL-2. Data are presented as mean ± SEM with n = 6. Coloured dots indicate data from individual donors across different stimulations. (D) Data representing the ratio of CD4+ T cells that have divided and express IFN-ɣ to total IFN-ɣ expressing CD4+ T cells. (E) IFN-ɣ mRNA expression in CD4+ T cells after 3 days culture with 1 μg/mL plate-bound anti-CD3 antibody + 1 μg/mL soluble anti-CD28 antibody was analysed by RT-qPCR. Data is presented relative to DMSO control set at 1 with n = 3 and shown as mean ± SEM. The significance of the data was evaluated by donor-matched one-way ANOVA with Dunnett’s multiple comparison test compared to DMSO control. *:p<0.05; **:p<0.005; ***:p<0.001.