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

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.