Characterization of monocyte-derived IFNalpha-generated dendritic cells.
The antitumor effects of IFNalpha is mainly mediated by the activation of cytotoxic T lymphocytes (CTLs), the activation of natural killer (NK) cells, and the generation of highly potent antigen-presenting dendritic cells (IFN-DCs). Recently, we demonstrated that these cells partially express the NK cell marker CD56 and reveal a direct cytotoxic immunity towards tumor cells. The aim of the present study was to explore these cells in more detail with respect to their phenotypical and functional characteristics. Flowcytometric analyses revealed that a 5-day incubation time of CD14+ monocytes with IFNalpha results in a steady increase of CD56 surface expression of these cells from 25% (+/-2%) on day 1 up to 68% (+/-11%) on day 5. Interestingly, additional culturing of negatively selected CD56- IFN-DCs also resulted in a partial CD56 surface expression. By comparing both cell types in more detail we found a significant decrease of CD14 expression on CD56+ IFN-DCs (66+/-6%) compared to CD56- IFN-DCs (76+/-6%). On the basis of functional tests, CD56+ IFN-DCs revealed a slightly increased phagocytosis capacity compared to CD56- IFN-DCs as only 82% of CD56- IFN-DCs showed a positive intracytoplasmatic signal after 60 minutes coculturing with FITC-labeled albumin, whereas 91% of CD56+ IFN-DCs were positive. Moreover, CD56+ IFN-DCs revealed a stronger T cell stimulation capacity compared to CD56- IFN-DCs. These results together with our previously described data suggest that CD56+ IFN-DCs and CD56- IFN-DCs may represent one identical cell population with different maturation status rather than two separate cell entities. Because of their high stimulating capacity and their direct cytolytic effects these cells represent a new promising tool for cellular anticancer therapy.
Jacobs
B
B
Department of Endocrinology, Diabetes, and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany.
Wuttke
M
M
Papewalis
C
C
Fenk
R
R
Stüssgen
C
C
Baehring
T
T
Schinner
S
S
Raffel
A
A
Seissler
J
J
Schott
M
M
D015415:Biomarkers / Q000097:blood; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis
D015415:Biomarkers; D019002:CD56 Antigen; D016898:Interferon-alpha