Effect of interleukin‐15 on anti‐CD3/anti‐CD28 induced apoptosis of umbilical cord blood CD4+ T cells

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Abstract
Objectives: Interleukin‐15 (IL‐15) has potential therapeutic advantage for patients receiving umbilical cord blood (CB) transplantation. The present study aims to examine the ability of IL‐15 to modulate the survival, maturation, and function of anti‐CD3/anti‐CD28 stimulated CB CD4+ T cells, in comparison with responses from adult peripheral blood (APB) CD4+ T cells.Methods: Enriched CB and APB CD4+ T cells were stimulated with anti‐CD3 and anti‐CD28 (anti‐CD3/anti‐CD28) in the presence or absence of IL‐15 (10 ng/mL) for 5 d. The percentages of apoptotic cells were assessed by propidium iodide/annexin‐V flow cytometric staining. T‐cell activation was analyzed with the expression of surface markers (CD45RO/CD69/CD25). Interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) production in culture supernatant was determined by enzyme‐linked immunosorbent assay.Results: CB CD4+ T cells had a higher survival and lower apoptotic response following anti‐CD3/anti‐CD28 stimulation, compared with APB CD4+ T cells. IL‐15 enhanced apoptosis and promoted CD45RO conversion of anti‐CD3/anti‐CD28 activated CB CD4+ T cells, an effect not observed with APB CD4+ T cells. Although activated CB CD4+ T cells expressed comparable level of CD69/CD25 expression to adults, IFN‐γ production of activated CB CD4+ T cells was markedly deficient compared with that of corresponding APB CD4+ T cells. Exogenous IL‐15 further enhanced the production of IFN‐γ, but not TNF‐α, of activated CB CD4+ T cells.Conclusions: 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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