Dendritic Cell Development in Culture from Thymic Precursor Cells in the Absence of Granulocyte/Macrophage Colony-stimulating Factor

The earliest lymphoid precursor population in the adult mouse thymus had previously been shown to produce not only T cells, but also dendritic cell (DC) progeny on transfer to irradiated recipients. In this study, culture of these isolated thymic precursors with a mixture of cytokines induced them to proliferate and to differentiate to DC, but not to T lineage cells. At least 70% of the individual precursors had the capacity to form DC. The resultant DC were as effective as normal thymic DC in the functional test of T cell stimulation in mixed leukocyte cultures. The cultured DC also expressed high levels of class I and class II major histocompatibility complex, together with CD11c, DEC-205, CD80, and CD86, markers characteristic of mature DC in general. However, they did not express CD8α or BP-1, markers characteristic of normal thymic DC. The optimized mixture of five to seven cytokines required for DC development from these thymic precursors did not include granulocyte/macrophage colony stimulating factor (GM-CSF), usually required for DC development in culture. The addition of anti–GM-CSF antibody or the use of precursors from GM-CSF–deficient mice did not prevent DC development. Addition of GM-CSF was without effect on DC yield when interleukin (IL) 3 and IL-7 were present, although some stimulation by GM-CSF was noted in their absence. In contrast, DC development was enhanced by addition of the Flt3/Flk2 ligand, in line with the effects of the administration of this cytokine in vivo. The results indicate that the development of a particular lineage of DC, probably those of lymphoid precursor origin, may be independent of the myeloid hormone GM-CSF.

[1]  A. Kelso,et al.  A subclass of dendritic cells regulates the response of naive CD8 T cells by limiting their IL-2 production. , 1996, Journal of immunology.

[2]  E. Maraskovsky,et al.  Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified , 1996, The Journal of experimental medicine.

[3]  K. Shortman,et al.  Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny , 1996, The Journal of experimental medicine.

[4]  K. Shortman,et al.  A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand- induced apoptosis , 1996, The Journal of experimental medicine.

[5]  Li Wu,et al.  CD4 and CD8 expression and T cell antigen receptor gene rearrangement in early intrathymic precursor cells , 1996, European journal of immunology.

[6]  D. Strunk,et al.  Generation of human dendritic cells/Langerhans cells from circulating CD34+ hematopoietic progenitor cells. , 1996, Blood.

[7]  K. Inaba,et al.  Dendritic cells as adjuvants for class I major histocompatibility complex-restricted antitumor immunity , 1996, The Journal of experimental medicine.

[8]  J. Banchereau,et al.  In Vitro Regulation of Dendritic Cell Development and Function , 1996 .

[9]  Li Wu,et al.  Early T lymphocyte progenitors. , 1996, Annual review of immunology.

[10]  A. Galy,et al.  Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. , 1995, Immunity.

[11]  T. Moore,et al.  T-cell lineage commitment and cytokine responses of thymic progenitors. , 1995, Blood.

[12]  M. Baggiolini Guidebook to cytokines and their receptors , 1995 .

[13]  K. Shortman,et al.  Induction of limited growth and differentiation of early thymic precursor cells by thymic epithelial cell lines. , 1995, Immunology letters.

[14]  Li Wu,et al.  Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation , 1995, European journal of immunology.

[15]  J. Banchereau,et al.  Activation of human dendritic cells through CD40 cross-linking , 1994, The Journal of experimental medicine.

[16]  R. Steinman,et al.  Proliferating dendritic cell progenitors in human blood , 1994, The Journal of experimental medicine.

[17]  A. Dunn,et al.  Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Simon C Watkins,et al.  Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony-stimulating factor and their maturational development in the presence of type-1 collagen , 1994, The Journal of experimental medicine.

[19]  K. Shortman,et al.  CD4 and CD8 expression by human and mouse thymic dendritic cells. , 1994, Immunology letters.

[20]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[21]  S. Carsons,et al.  Mechanisms of tumor necrosis factor-granulocyte-macrophage colony-stimulating factor-induced dendritic cell development. , 1993, Blood.

[22]  S. Nishikawa,et al.  Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation , 1993, The Journal of experimental medicine.

[23]  Li Wu,et al.  Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population , 1993, Nature.

[24]  R. Steinman,et al.  Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Steinman,et al.  Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor , 1992, The Journal of experimental medicine.

[26]  J. Banchereau,et al.  GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells , 1992, Nature.

[27]  J. Tikerpae,et al.  Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. , 1992, Journal of immunology.

[28]  M. Mehlig,et al.  Dendritic cells from mouse bone marrow: in vitro differentiation using low doses of recombinant granulocyte-macrophage colony-stimulating factor. , 1992, Journal of immunological methods.

[29]  Li Wu,et al.  The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells , 1992, The Journal of experimental medicine.

[30]  R. Steinman,et al.  Identification of proliferating dendritic cell precursors in mouse blood , 1992, The Journal of experimental medicine.

[31]  N. Heveker,et al.  Development of a Langerhans cell phenotype from peripheral blood monocytes. , 1992, Immunology letters.

[32]  M. Antica,et al.  Developmental potential of the earliest precursor cells from the adult mouse thymus , 1991, The Journal of experimental medicine.

[33]  Li Wu,et al.  CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus , 1991, Nature.

[34]  R. Steinman,et al.  The dendritic cell system and its role in immunogenicity. , 1991, Annual review of immunology.

[35]  J. Tikerpae,et al.  Identification of hematopoietic progenitors of macrophages and dendritic Langerhans cells (DL-CFU) in human bone marrow and peripheral blood. , 1990, Blood.

[36]  H. Drexhage,et al.  Accessory cells with a morphology and marker pattern of dendritic cells can be obtained from elutriator-purified blood monocyte fractions. An enhancing effect of metrizamide in this differentiation. , 1989, Immunobiology.

[37]  G. Nossal,et al.  The Walter and Eliza Hall Institute of Medical Research , 1996, The Medical journal of Australia.