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-a-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. Westernblot analysis shows that IL-15 Ra is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL-15 significantly enhanced CB IL-15 Ra 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. Am.

IL-15 preferentially resulted in an activation-enhancing effect on CB CD4+ T cells, accompanied by increased apoptosis. Our finding may have therapeutic implications while designing IL-15 immunotherapy for patients receiving CB transplant.

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