Figure 3. Combined IL-2 and IL-4 increase the suppressive ability of Tregs.
(A–C) Proliferation (flow cytometry) and cytokine output (ELISA) of freshly isolated and Celltrace-stained Tconv co-cultured with αCD3ε and the indicated ratios of WT Tregs separately and previously stimulated with αCD3ε and all cytokine conditions for 3 days, washed, and normalized for cell number at the time of co-culture. The flow histograms were gated on Tconv cells. N = 3 for all graphs and histograms are representative. (D–F) Proliferation (flow cytometry) and cytokine production (ELISA) of freshly isolated Tconv cells co-cultured with αCD3ε and the indicated ratios of IL-10-/- Tregs separately and previously stimulated with αCD3ε and all cytokine conditions for 3 days, washed, and normalized for cell number at the time of co-culture. The flow histograms were gated on Tconv cells. N = 3 for all graphs and histograms are representative. (G–I) Proliferation (flow cytometry) and cytokine production (ELISA) of freshly isolated Tconv cells from WT mice co-cultured with αCD3ε and the indicated ratios of IL-10 cKO Tregs separately and previously stimulated with αCD3ε and all cytokine conditions for 3 days, then washed. The flow histograms were gated on Tconv cells. N = 3 for all graphs and histograms are representative. (J–L) Proliferation (flow cytometry) and cytokine production (ELISA) of freshly isolated Tconv cells co-cultured with αCD3ε and the indicated ratios of WT Tregs separately and previously stimulated with αCD3ε and all cytokine conditions for 7 days. Co-culture ratio was based on the number of Tregs prior to cytokine stimulation to incorporate their proliferation. The flow histograms were gated on Tconv cells. N = 3 for all graphs and histograms are representative. (M) Percentage of the overall culture comprising of WT or IL-10 cKO Tregs and Tconv over the course of time as determined by flow cytometry. The Tregs were purified and stimulated with αCD3ε and all cytokine conditions for 3 days, washed, then placed in co-culture with freshly isolated Tconv cells at a 1:8 Treg:Tconv starting ratio (line). N = 3. For all panels, mean ± SEM are indicated. *p<0.05, ****p<0.0001.