The gp130-stimulating designer cytokine hyper-IL-6 promotes the expansion of human hematopoietic progenitor cells capable to differentiate into functional dendritic cells

Objective. Hyper-IL-6, a fusion protein of interleukin-6 and its specific receptor, together with stem cell factor leads to the proliferation of primitive hematopoietic progenitor cells. Based on these findings, the current study examined whether hyper-IL-6 promotes the growth of precursor cells that can be further differentiated into dendritic cells in the presence of additional cytokines. Methods. Dendritic cell cultures were generated from CD34+ hematopoietic progenitor cells derived either from bone marrow or from peripheral blood. CD34+ cells were cultured in the presence of cytokines for 2 weeks and then used for phenotyping and T-cell stimulation assays. Results. Hyper-IL-6 in the presence of stem cell factor induced a 60- to 80-fold expansion of CD34+ progenitor cells following 2 weeks of culture in serum-free medium. The addition of granulocyte-macrophage colony-stimulating factor to hyper-IL-6 and stem cell factor was essential for the differentiation of expanded progenitor cells into antigen presenting cells capable of inducing a primary T-cell response to soluble protein, which is a typical feature of dendritic cells. Phenotypic analyses confirmed the expansion of immature dendritic cells, which could be further differentiated into mature CD83+ dendritic cells under the influence of interleukin-4, interleukin-1β, tumor necrosis factor-α, and prostaglandin E2. The capacity of expanded dendritic cells to stimulate protein-specific CD4+ T cells was used to stimulate a primary T-helper cell response to the recombinant protein of the hepatitis-B core antigen in healthy donors. Conclusion. The expansion and differentiation of functional dendritic cells from CD34+ progenitor cells under serum-free culture conditions allow for the possibility to develop more effective ways to immunize against viral infections and tumor diseases.