Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines.
Although antigen-loaded dendritic cells (DC) are being investigated as antitumor vaccines, which DC differentiation state is most effective is not clear. Three DC functions that may be critical for immunization potential are expression of CD80/86, cytokine production following CD40 engagement, and migration to chemokine receptor 7-binding chemokines. We therefore examined highly purified human monocyte-derived immature and mature DC for these properties from normal donors and cancer patients. Although high expression of CD80/86 and migration to 6Ckine + macrophage-inflammatory protein-3beta were properties of mature DC, cytokine production following CD40 ligation was superior by immature DC. Loss of cytokine secretion occurred with multiple maturation conditions, was not apparently reversible, and was also seen with lipopolysaccharide stimulation in correlation with down-regulated Toll-like receptor expression. Our results suggest that the functions thought to contribute to optimal T cell priming are not coexpressed by the same DC population and that immature and mature DC likely possess distinct CD40-mediated signaling events.
Tschoep
Katharina
K
Department of Pathology, Section of Hematology/Oncology, University of Chicago, Illinois, USA. tgajewsk@medicine.bsd.uchicago.edu
Manning
Thomas C
TC
Harlin
Helena
H
George
Christopher
C
Johnson
Melissa
M
Gajewski
Thomas F
TF
D015703:Antigens, CD / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D022423:Myeloid Cells; D009369:Neoplasms / Q000473:pathology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine
D015703:Antigens, CD; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016207:Cytokines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine