ISOLATION OF HUMAN BLOOD DENDRITIC CELLS USING THE CMRF-44 MONOCLONAL-ANTIBODY - IMPLICATIONS FOR STUDIES ON ANTIGEN-PRESENTING CELL-FUNCTION AND IMMUNOTHERAPY

Dendritic cells (DC) are potent antigen-presenting cells (APC) with th e capacity to stimulate a primary T lymphocyte immune response and are therefore of interest for potential immunotherapeutic applications, F reshly isolated DC or DC precursors may be preferable for studies of a ntigen uptake and the potential control of APC costimulator activity. In this report, we report that the monoclonal antibody CMRF-44 can be used to detect early DC differentiation, The majority of DC circulatin g in blood do not express any known DC lineage specific markers, but c an be identified by CMRF-44 labeling after a brief period of in vitro Culture, The sequential acquisition of DC activation antigens allows t he identification of hive stages of DC maturation/activation. Cytokine s, especially granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF)alpha, enhance both phases of this pr ocess, whereas CD40-ligand trimer preferentially enhances the final DC maturation to a fully mature, activated phenotype, DC positively sele cted using CMRF-44 possess potent allostimulatory activity and are eff icient at the uptake, processing, and presentation of soluble antigens for both primary and secondary immune responses, CMRF-44(+) DC are al so more potent than other APC types at restimulation of a chronic myel oid leukemia peptide specific T-cell clone. The use of a purified popu lation of freshly isolated DC may be advantageous in attempts to initi ate, maintain, and direct immune responses for immunotherapeutic appli cations. (C) 1997 by The American Society of Hematology.