Methodological Insights Into T-Cell Activation: CD3/CD28 Versus PMA/Ionomycin Stimulation.

PMA/ionomycin and CD3/CD28 stimulation induce fundamentally distinct signaling programs in primary human T cells. While CD3/CD28 stimulation activates both ERK and IL-2/STAT5 signaling pathways, PMA/ionomycin induces predominantly ERK-dependent proliferation despite robust IL-2 production and CD25 upregulation. These findings highlight important mechanistic and methodological differences between pharmacological and receptor-mediated T-cell activation.