학술논문

Development of Immunogenic Tumor-Loaded Dendritic Cells Through Physical Perturbation and Apoptotic Cell Loading.
Document Type
Article
Source
Immunological Investigations. Nov2008, Vol. 37 Issue 8, p798-821. 24p. 1 Diagram, 6 Graphs.
Subject
*DENDRITIC cells
*MONOCYTES
*APOPTOSIS
*CELL growth
*TUMORS
Language
ISSN
0882-0139
Abstract
To improve understanding of the forces that drive monocytes to transition into dendritic cells (Liyanage et al., 2002), we developed an experimental system that converts monocytes to DC by passage of leukocytes through a 400 μm silica bead column. The results demonstrate that overnight culture of column-treated monocytes causes a phenotypic conversion that is characteristically displayed by immature DC. These phenotypic changes were enhanced when the DC were loaded with apoptotic cells, leading to increased expression of the DC maturation-associated markers CD83, CD80 and the chemokine receptor CCR7. The DC demonstrated potent induction of allogeneic T cell proliferation and the capacity to activate autologous CD8+ T cells. The CD8 T cells expressed augmented levels of perforin, IFN-γ and TNF-α and mediated CTCL cell apoptosis. These studies demonstrate that physical contact with silica beads combined with loading of apoptotic tumor cells induces synchronized, rapid conversion of human monocytes to DC, which can efficiently stimulate CD8+ T cells. These results may aid in the development of more efficient DC vaccines that can be loaded with the universe of antigens available in apoptotic tumor cells in a rapid, clinically practical fashion. [ABSTRACT FROM AUTHOR]