Summary:Decreased graft-versus-host disease (GVHD) in cord blood (CB) transplantation may be attributed to the immunological immaturity and susceptibility to apoptosis of CB mononuclear cells (MNCs). Cytokines like interleukin (IL)-12 and IL-15 may be used for in vivo administration or ex vivo expansion of lymphoid cells for more rapid recovery following stem cell transplant, and for providing a graft-versus-leukemia (GVL) effect. We investigated the effects of IL-12 and IL-15, alone or in combination on apoptosis and proliferation of both CB and adult peripheral blood ( used as an alternative to bone marrow for transplants in children with immunological and hematological disorders.1,2 A recent study established that recipients of CB transplants from HLA-identical siblings had a lower incidence of acute and chronic GVHD than recipients of BM transplant from HLA-identical siblings.3 Expansion and activation of cord blood cells by cytokines might greatly benefit patients undergoing stem cell transplantation by increasing resistance against viral infections and providing graft-versus-leukemia (GVL) effects through enhancement of cytotoxic T lymphocyte function and natural killer (NK) activity. 4,5 Interleukin (IL)-12 is a 75 kDa heterodimeric protein that is secreted by macrophages, monocytes and dendritic cells, and stimulates NK and T cells. 6 Another recently cloned cytokine, IL-15, using the  and ␥ c subunits of the IL-2 receptor (IL-2R) complex and a unique ␣ chain for binding and signal transduction, also played an important role in enhancing various lymphocyte functions, including T and NK cytotoxicity.7 The IL-15R has a broader tissue distribution than IL-2R, as the expression of IL-15 mRNA has been detected in placenta, skeletal muscle, and activated monocytes. 7,8 The level of mRNA expression and production of both IL-12 and IL-15 have been shown to be decreased in CB MNCs compared to that in adult MNCs. 9 We have previously demonstrated the ability of IL-12 and IL-15 in enhancing various NK cytolytic functions and CD16/56 expression in cord blood and in HIV-infected subjects. [10][11][12] UCB T cells and NK cells have a potential to proliferate as strongly as adult peripheral blood (APB) lymphocytes upon stimulation with cytokines.13 Several studies examined the immunological nature of UCB lymphocytes and showed that programmed cell death (apoptosis) is a key phenomenon for immunological tolerance or anergy, 14,15 thereby contributing to the lower incidence of GVHD. Previous studies have shown that UCB cells had low levels of expression of CD95 and CD95 ligand,16 in comparison with APB MNCs, and were resistant to apoptosis upon primary simulation with anti-CD3 monoclonal antibody. However, they are much more likely to be induced to apoptose by allo-priming than adult lymphocytes. 17 Although the ability of IL-12 and IL-15 to augment proliferation and activation of CB MNCs is well documented, their effect on apoptosis of CB MNCs has not been well characterized.