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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) 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-gamma 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-gamma, but not TNF-alpha, 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.
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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) 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-gamma 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-gamma, but not TNF-alpha, 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.
Authors: Lisa Marie Serrano; Timothy Pfeiffer; Simon Olivares; Tontanai Numbenjapon; Jennifer Bennitt; Daniel Kim; David Smith; George McNamara; Zaid Al-Kadhimi; Joseph Rosenthal; Stephen J Forman; Michael C Jensen; Laurence J N Cooper Journal: Blood Date: 2005-12-13 Impact factor: 22.113
Authors: Guillemette X Masse; Erwan Corcuff; Hélène Strick-Marchand; Delphine Guy-Grand; Anna Tafuri-Bladt; Matthew L Albert; Olivier Lantz; James P Di Santo Journal: Proc Natl Acad Sci U S A Date: 2007-09-12 Impact factor: 11.205