While activating and expanding cell populations in the lab, it’s common to experience activation-induced cell death. This is caused by the natural apoptosis mechanism that lies genetically within effector cells.
Specifically, effector cells express Fas or a TNF (tumor necrosis factor) receptor, which binds to a death factor, such as Fas Ligand, a ceramide, or ROS (reactive oxygen species.) Directly following activation, the expression of Fas is upregulated, causing T cells to express Fas after binding to TCR. At this point, these effector cells could be triggered into activation-induced apoptosis by Fas Ligand, an apoptotic protein.
Cell therapies, such as CAR T cell therapies, and tumor-infiltrating cell therapies are more successful on smaller tumors. Large tumors have a high T cell demand from the body and require constant expansion and proliferation. Constant artificial stimulation of T cells can increase the rate at which Fas is upregulated, increasing the rate of AICD, or apoptosis.
Activation-Induced Cell Death T Cells
Fas and Fas Ligands are vital components of the overall mechanism controlling effector cell survival and death. The regulation, expression, and abundance of these receptors and proteins dictate the number of active effector cells in the body.
Properly functioning activation-induced cell death provides a necessary safeguard against uncontrolled T cell activation, proliferation, and inflammatory response. Too high a rate of any of these cellular phenomena can result in complications like cancer and autoimmune diseases.
IL-2 Activation-Induced Cell Death
IL-2, or interleukin-2, is a cytokine produced by multiple immune cells,  such as T cells. IL-2 aids in the development of the immune system and increases the activity of T and B cells.
In addition to its part in activation and maturation, IL-2 also induces apoptosis in some late-stage effector cells. Playing a vital role in activation-induced cell death, IL-2 guides the elimination of self-reactive or auto-reactive T cells. This ability to initiate apoptosis in immune cells is considered proapoptotic. IL-2 is also responsible for diminishing memory effector cell count and increasing cell cycling.