Generation of immunostimulatory dendritic cells from human CD34+ hematopoietic progenitor cells of the bone marrow and peripheral blood
| Autor: | H, Bernhard, M L, Disis, S, Heimfeld, S, Hand, J R, Gralow, M A, Cheever |
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| Rok vydání: | 1995 |
| Předmět: |
Antigen Presentation
Receptor ErbB-2 Tumor Necrosis Factor-alpha Macrophages T-Lymphocytes Histocompatibility Antigens Class II Granulocyte-Macrophage Colony-Stimulating Factor Antigens CD34 Bone Marrow Cells Dendritic Cells Hematopoietic Stem Cells Lymphocyte Activation Peptide Fragments Stimulation Chemical Phenotype Antigens CD Bone Marrow B7-1 Antigen Leukocytes Mononuclear Humans Cells Cultured |
| Zdroj: | Cancer research. 55(5) |
| ISSN: | 0008-5472 |
| Popis: | Dendritic antigen-presenting cells are considered to be the most effective stimulators of T cell immunity. The use of dendritic cells has been proposed to generate therapeutic T cell responses to tumor antigens in cancer patients. One limitation is that the number of dendritic cells in peripheral blood is exceedingly low. Dendritic cells originate from CD34+ hematopoietic progenitor cells (HPC) which are present in the bone marrow and in small numbers in peripheral blood. CD34+ HPC can be mobilized into the peripheral blood by in vivo administration of granulocyte-colony-stimulating factor. The aim of the current study was to determine whether functional dendritic cells could be elicited and grown in vitro from CD34+ HPC derived from bone marrow or granulocyte-colony-stimulating factor-mobilized peripheral blood. Culture of CD34+ HPC with granulocyte-macrophage-colony-stimulating factor and tumor necrosis factor alpha yielded a heterogeneous cell population containing cells with typical dendritic morphology. Phenotypic studies demonstrated a loss of the CD34 molecule over 1 week and an increase in cells expressing surface markers associated with dendritic cells, CD1a, CD80 (B7/BB1), CD4, CD14, HLA-DR, and CD64 (Fc gamma RI). Function was validated in experiments showing that cultured cells could stimulate proliferation of allogeneic CD4+ and CD8+ T lymphocytes. Antigen-presenting capacity was further confirmed in experiments showing that cultured cells could effectively stimulate tetanus toxoid-specific responses and HER-2/neu peptide-specific responses. The derivation and expansion of dendritic cells from cultured bone marrow or granulocyte-colony-stimulating factor-mobilized CD34+ HPC may provide adequate numbers for testing of dendritic cells in clinical studies, such as vaccine and T cell therapy trials. |
| Databáze: | OpenAIRE |
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