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 r eceptor, together with stem cell factor leads to the proliferation of primi tive hematopoietic progenitor cells. Based on these findings, the current s tudy examined whether hyper-IL-6 promotes the growth of precursor cells tha t can be further differentiated into dendritic cells in the presence of add itional 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 th en 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-stimulati ng factor to hyper-IL-6 and stem cell factor was essential for the differen tiation of expanded progenitor cells into antigen presenting cells capable of inducing a primary T-cell response to soluble protein, which is a typica l feature of dendritic cells. Phenotypic analyses confirmed the expansion o f immature dendritic cells, which could be further differentiated into matu re CD83(+) dendritic cells under the influence of interleukin-4, interleuki n-1 beta, tumor necrosis factor-alpha, and prostaglandin E-2. The capacity of expanded dendritic cells to stimulate protein-specific CD4(+) T cells wa s used to stimulate a primary T-helper cell response to the recombinant pro tein 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 fo r the possibility to develop more effective ways to immunize against viral infections and tumor diseases. (C) 2000 International Society for Experimen tal Hematology. Published by Elsevier Science Inc.