Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines

Journal of Leukocyte Biology

Helena Harlin²  Melissa Johnson²  Katharina Tschoep²  Thomas F. Gajewski¹  Thomas C. Manning²  Christopher George³ 

[1] Pathology and Medicine, Section of Hematology/Oncology, University of Chicago, Illinois Pathology and Pathology and Medicine, Section of Hematology/Oncology, University of Chicago, Illinois Medicine, Section of Hematology/Oncology, University of Chicago, Illinois Pathology and Medicine, Section of Hematology/Oncology, University of Chicago, Illinois;Pathology and Pathology and Pathology and;Medicine, Section of Hematology/Oncology, University of Chicago, Illinois Medicine, Section of Hematology/Oncology, University of Chicago, Illinois Medicine, Section of Hematology/Oncology, University of Chicago, Illinois

关键词: IL-12;    cancer;    immunotherapy;    CD40;    antigen-presenting cells;    chemokines;   

DOI  :  10.1189/jlb.0702352

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-3β 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.

【 授权许可】

Unknown