Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0702352 on May 22, 2003

Published online before print May 22, 2003
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(Journal of Leukocyte Biology. 2003;74:69-80.)
© 2003 by Society for Leukocyte Biology

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

Katharina Tschoep*, Thomas C. Manning*, Helena Harlin*, Christopher George{dagger}, Melissa Johnson* and Thomas F. Gajewski*,{dagger}

Departments of
* Pathology and
{dagger} Medicine, Section of Hematology/Oncology, University of Chicago, Illinois

Correspondence: Thomas F. Gajewski, M.D., Ph.D., University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637. E-mail: tgajewsk{at}medicine.bsd.uchicago.edu

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-3ß 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.

Key Words: IL-12 • cancer • immunotherapy • CD40 • antigen-presenting cells • chemokines




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