Han, P.Story, C.McDonald, T.Mrozik, K.Snell, L.2006-06-232006-06-232002Cytotherapy, 2002; 4(2):165-1751465-32491477-2566http://hdl.handle.net/2440/7175<h4>Background</h4>Pre-B ALL cells generally elicit a weak immune host response, due to poor expression of co-stimulatory molecules and/or suppression of immune function. A possible way to enhance immunogenicity of pre-B ALL cells is to convert them to DC-like cells.<h4>Methods</h4>To study the effect of ALL cells on T-cell function, ALL cells were incubated with T adult cells activated by OKT3 MAb. Liquid culture of de novo pre-B ALL cells for 7 days, in a medium containing IL-1alpha, IL-3, IL-7, Flt 3 ligand (L) and tumor-necrosis factor alpha (TNF-alpha) produced DC-like cells. These were evaluated for morphology, viability, phenotype, as measured by flow cytometry, and function, including MLR.<h4>Results</h4>Pre-B ALL cell-lines NALM-6, BALM and de novo pre-B ALL cells failed to stimulate T cells, but suppressed stimulated T cells. The DC-like cells displayed characteristic features of DCs: filiform cytoplasmic projections, and phenotypic expression of co-stimulatory molecules CD80/86, MHC Class I and II molecules, CD83 and CD1a. Genetic monoclonality study confirmed their leukemic origin. In a 5-day MLR culture, the DC-like cells potently activated allogeneic adult and cord CD4+ and CD8+ T cells. Furthermore, both CD4+ and CD8+ T cells were primed towards a Type I. No such effect was seen with unmanipulated de novo pre-B ALL cells.<h4>Discussion</h4>DC-like cells can be generated from childhood pre-B ALL cells and are potent stimulators of adult and naïve cord CD8+ T cells via CD4+ cells. These cells may form part of an immunotherapy strategy to overcome tolerance to ALL cells.enB-LymphocytesDendritic CellsT-LymphocytesHematopoietic Stem CellsCell LineHumansImmunotherapyFlow CytometryCell CycleCell DifferentiationPrecursor Cell Lymphoblastic Leukemia-LymphomaJournal article002002048610.1080/1465324023173818750001759311000082-s2.0-003600060260361Mrozik, K. [0000-0002-4890-8208]