EFFICIENT PRESENTATION OF SOLUBLE-ANTIGEN BY CULTURED HUMAN DENDRITICCELLS IS MAINTAINED BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR PLUS INTERLEUKIN-4 AND DOWN-REGULATED BY TUMOR-NECROSIS-FACTOR-ALPHA

Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and in terleukin 4 we have established dendritic cell (DC) lines from blood m ononuclear cells that maintain the antigen capturing and processing ca pacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histo compatibility complex (MHC) class I and class II molecules, CD1, Fcgam maRII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are hig hly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs ar e as efficient as antigen-specific B cells in presenting tetanus toxoi d (TT) to specific T cell clones. Their efficiency of antigen presenta tion can be further enhanced by specific antibodies via FcR-mediated a ntigen uptake. Incubation of these cultured DCs with tumor necrosis fa ctor alpha (TNF-alpha) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class 11 molecu les, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice va riant (CD44-v9); by contrast, FcgammaRII is markedly and sometimes com pletely downregulated. The functional consequences of the short contac t with TNF-alpha are an increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold de crease in presentation of TT-immunoglobulin G complexes.