Differential effect of IL-15 and IL-2 on survival of phytohemagglutinin- activated umbilical cord blood T cells

Cytokine immunotherapy using interleukin (IL)-2 and IL-15 may be beneficial for patients receiving umbilical cord blood (CB) transplantation by ameliorating post-transplant T-cell apoptosis. The present study compares the differential effect of IL-15 and IL-2 on survival of phytohemagglutinin (PHA)-activated CB and adult peripheral blood (APB) T lymphocytes. In comparison with IL-2, IL-15 preferentially enhanced the survival of CB PHA-activated T cells by decreasing the caspase-3⁺ population and by increasing the Bcl-2⁺ population. Activated CB T cells were more susceptible to TNF-α-induced apoptosis compared to their adult counterparts. However, the susceptibility could be abrogated by IL-15 but not by IL-2. IL-15 but not IL-2 down-regulated CD28 expression on both activated CB and APB CD8⁺ T cells, with a much greater effect seen with CB. Western-blot analysis shows that IL-15 Rα is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL-15 significantly enhanced CB IL-15 Rα expression to levels comparable to that of adults. Thus, IL-15 may provide a better therapeutic choice for immune reconstitution than IL-2 post-CB transplantation due to its preferential survival enhancing effect on CB T cells.