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Interleukin-15 Enhances CD4+ CD45RA+ Expression on Umbilical Cord Blood Mononuclear Cells

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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 naïve 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+ 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 fresh CB MNCs, IN-15 exerted a dose-dependent increase of % CD45RA+ /CD4+ in CB MNCs, an effect not observed with APB MNCs treated with IL-15. The percentages of CD45RA+ and CDRO+ 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 the that achieved in APB MNCs. The adility 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.

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