Interleukin-15 enhances CD4⁺ CD45RA⁺ expression on umbilical cord blood mononuclear cells

The reduced incidence of graft-vs.-host disease following umbilical cord blood (CB) transplantation may be related to the functional immaturity of newborn T cells expressing mainly the naive CD45RA phenotype. Expansion of CD4⁺ CD45RA⁺ T cells using cytokines may benefit neonates and infants with human immunodeficiency virus (HIV) infection, as a preferential decline in CD4⁺ CD45RA⁺ cells has been noted as HIV disease progresses. The aim of the study was to investigate the effect of interleukin (IL)-15, a novel cytokine similar to IL-2 in biological activities, on CD45RA/RO expression and apoptosis in umbilical cord blood (CB) and adult peripheral blood (APB) mononuclear cells (MNCs). Prior to culture, CB MNCs contained a greater number of CD4⁺ CD45RA⁺ cells and fewer CD4⁺ CD45RO⁺ cells than did APB MNCs. When incubated with RPMI-1640 containing 10% fetal calf serum for 7 days, the percentage of CD45RA⁺ cells within CD4⁺ T cells (%CD45RA⁺/CD4⁺) significantly decreased compared to that of fresh CB MNCs. IL-15 exerted a dose-dependent increase of %CD45RA⁺/CD4⁺ and a corresponding decrease of %CD45RO⁺/CD4⁺ in CB MNCs, an effect not observed with APB MNCs treated with IL-15. The percentages of CD45RA⁺ and CD45RO⁺ expression within CD8⁺ cells, however, were not influenced by IL-15, in either CB or APB MNCs. A greater number of CB MNCs underwent apoptosis than did APB MNCs after 7 days of culture in RPMI-1640 containing 10% fetal calf serum. IL-15 did not inhibit apoptosis but induced proliferation comparable to that achieved in APB MNCs. The ability of IL-15 to preferentially enhance the proliferation of CD4⁺ CD45RA⁺ cells in CB MNCs suggests a role for immunomodulative therapy in HIV-infected newborns and infants.