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© The Rockefeller University Press, 0022-1007/1998/4/1019/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 7, April 6, 1998 1019-1028

Articles

Neutrophil Granulocyte–committed Cells Can Be Driven to Acquire Dendritic Cell Characteristics

Leopold Oehler*,{ddagger}, Otto Majdic*, Winfried F. Pickl*, Johannes Stöckl*, Elisabeth Riedl*, Johannes Drach§, Klemens Rappersberger||, Klaus Geissler{ddagger}, and Walter Knapp*

From the * Institute of Immunology, the Department of Internal Medicine I, the {ddagger} Division of Hematology, the § Division of Oncology, and the || Department of Dermatology, University of Vienna, A-1090 Vienna, Austria

Polymorphonuclear granulocytes (PMNs) are thought to fulfill their role in host defense primarily via phagocytosis and release of cytotoxic compounds and to be inefficient in antigen presentation and stimulation of specific T cells. Dendritic cells (DCs), in contrast, are potent antigen-presenting cells with the unique capacity to initiate primary immune responses. We demonstrate here that highly purified lactoferrin-positive immediate precursors of end-stage neutrophilic PMN (PMNp) can be reverted in their functional maturation program and driven to acquire characteristic DC features. Upon culture with the cytokine combination granulocyte/macrophage colony-stimulating factor plus interleukin 4 plus tumor necrosis factor {alpha}, they develop DC morphology and acquire molecular features characteristic for DCs. These molecular changes include neo-expression of the DC-associated surface molecules cluster of differentiation (CD)1a, CD1b, CD1c, human leukocyte antigen (HLA)-DR, HLA-DQ, CD80, CD86, CD40, CD54, and CD5, and downregulation of CD15 and CD65s. Additional stimulation with CD40 ligand induces also expression of CD83 and upregulates CD80, CD86, and HLA-DR. The neutrophil-derived DCs are potent T cell stimulators in allogeneic, as well as autologous, mixed lymphocyte reactions (MLRs), whereas freshly isolated neutrophils are completely unable to do so. In addition, neutrophil-derived DCs are at least 10,000 times more efficient in presenting soluble antigen to autologous T cells when compared to freshly isolated monocytes. Also, in functional terms, these neutrophil-derived DCs thus closely resemble "classical" DC populations.

Address correspondence to Walter Knapp, Institute of Immunology, University of Vienna, Borschkegasse 8A, A1090 Vienna, Austria. Phone: 43-1-40154-350; Fax: 43-1-4086670; E-mail: walter.knapp{at}univie.ac.at

1 Abbreviations used in this paper: CD, cluster of differentiation; CD40L, CD40 ligand; CML. chronic myeloid leukemia; DC, dendritic cell; HLA, human leukocyte antigen; LF, lactoferrin; md-DC, monocyte-derived DC; MLR, mixed lymphocyte reaction; MPO, myeloperoxidase; PMNp, PMN granulocyte precursor; rh, recombinant human; TT, tetanus toxoid.


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