NEUTROPHIL GRANULOCYTE-COMMITTED CELLS CAN BE DRIVEN TO ACQUIRE DENDRITIC CELL CHARACTERISTICS

Polymorphonuclear granulocytes (PMNs) are thought to fulfill their rol e in host defense primarily via phagocytosis and release of cytotoxic compounds and to be inefficient in antigen presentation and stimulatio n 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) ca n be reverted in their functional maturation program and driven to acq uire characteristic DC features. Upon culture with the cytokine combin ation granulocyte/macrophage colony-stimulating factor plus interleuki n 4 plus tumor necrosis factor alpha, they develop DC morphology and a cquire molecular features characteristic for DCs. These molecular chan ges include neo-expression of the DC-associated surface molecules clus ter of differentiation (CD)1a, CD1b, CD1c, human leukocyte antigen (HL A)-DR, HLA-DQ, CD80, CD86, CD40, CD54, and CD5, and downregulation of CD15 and CD65s. Additional stimulation with CD40 ligand induces also e xpression of CD83 and upregulates CD80, CD86, and HLA-DR. The neutroph il-derived DCs are potent T cell stimulators in allogeneic, as well as autologous, mixed lymphocyte reactions (MLRs), whereas freshly isolat ed neutrophils are completely unable to do so. In addition, neutrophil -derived DCs are at least 10,000 times more efficient in presenting so luble antigen to autologous T cells when compared to freshly isolated monocytes. Also, in functional terms, these neutrophil-derived DCs thu s closely resemble ''classical'' DC populations.