FROM SENTINEL TO MESSENGER - AN EXTENDED PHENOTYPIC ANALYSIS OF THE MONOCYTE TO DENDRITIC CELL TRANSITION

The transitional stages in the relationship between sentinel monocytes and messenger dendritic cells that are active in adaptive immunity, a re, as yet, unclear. To explore these events, 2-hr adherent peripheral blood mononuclear cells were used either as monocytes, or cultured fo r 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF ) and interleukin-4 (IL-4) to generate dendritic cells, and the phenot ypic features and relationship of the two cell populations was investi gated using an extensive panel of monoclonal antibodies (mAbs). The fe atures of the shift from monocyte to dendritic cell were also examined by daily phenotyping during the 7-day culture period. Twenty-five mAb s, most of which recognized known CD molecules, bound both monocytes a nd dendritic cells equally, whereas 19 mAbs exhibited differential sta ining. Four molecules not previously reported on dendritic cells were documented: CD87, CD98, CD147 and CD148. Seven cell-surface molecules (HLA-DQ, CD1a, CD13, CD30, CD43, CD63 and CD86) were expressed either at very low levels or not at all on monocytes, but had a strikingly in creased expression on dendritic cells, suggesting a role in antigen pr esentation. The kinetics of monocyte to dendritic cell transition reve aled a rapid activation phase within the first 24 hr, with a considera ble increase in expression of the activation markers HLA-DR, CD13, CD1 4 and CD98; this was followed by a down-regulation of CD14 and a more gradual development of the other dendritic cell features over the rema ining 6 days, with steady increases in CD1a, CD18, CD43, CD86, HLA-DR and HLA-DQ. Thus, these studies have demonstrated four novel component s of the dendritic cell, and have documented the dynamic multistep nat ure of the process whereby an antigen-presenting dendritic cell phenot ype may emerge from a monocyte precursor.