Horm Metab Res 2008; 40(2): 117-121
DOI: 10.1055/s-2007-1022564
Original

© Georg Thieme Verlag KG Stuttgart · New York

Characterization of Monocyte-derived IFNα-generated Dendritic Cells

B. Jacobs 1 , M. Wuttke 1 , C. Papewalis 1 , R. Fenk 2 , C. Stüssgen 1 , T. Baehring 1 , S. Schinner 1 , A. Raffel 3 , J. Seissler 4 , M. Schott 1
  • 1Department of Endocrinology, Diabetes, and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany
  • 2Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Duesseldorf, Germany
  • 3Department of General and Visceral Surgery, University Hospital Duesseldorf, Germany
  • 4Medical Clinic Innenstadt, Ludwig-Maximilians-University Munich, Germany
Further Information

Publication History

received 07.12.2007

accepted 21.12.2007

Publication Date:
19 February 2008 (online)

Abstract

The antitumor effects of IFNα 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 IFNα 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.

References

  • 1 Gutterman JU. Cytokine therapeutics: lessons from interferon alpha.  Proc Natl Acad Sci USA. 1994;  91 1198-1205
  • 2 Pfeffer LM, Dinarello CA, Herberman RB, Williams BR, Borden EC, Bordens R, Walter MR, Nagabhushan TL, Trotta PP, Pestka S. Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons.  Cancer Res. 1998;  58 2489-2499
  • 3 Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S, Antonenko S, Liu YJ. The nature of the principal type 1 interferon-producing cells in human blood.  Science. 1999;  284 1835-1837
  • 4 Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, Waal MR de, Liu YJ. Reciprocal control of T helper cell and dendritic cell differentiation.  Science. 1999;  283 1183-1186
  • 5 Sun S, Zhang X, Tough DR, Sprent J. Type I interferon-mediated stimulation of T cells by CpG DNA.  J Exp Med. 1998;  188 2335-2342
  • 6 Marrack P, Kappler J, Mitchell T. Type I interferons keep activated T cells alive.  J Exp Med. 1999;  189 521-530
  • 7 Kolumam GA, Thomas S, Thompson LJ, Sprent J, Murali-Krishna K. Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection.  J Exp Med. 2005;  202 637-650
  • 8 Trinchieri G, Santoli D. Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis.  J Exp Med. 1978;  147 1314-1333
  • 9 Griffith TS, Wiley SR, Kubin MZ, Sedger LM, Maliszewski CR, Fanger NA. Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL.  J Exp Med. 1999;  189 1343-1354
  • 10 Santini SM, Lapenta C, Logozzi M, Parlato S, Spada M, Di Pucchio T, Belardelli F. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice.  J Exp Med. 2000;  191 1777-1788
  • 11 Fanger NA, Maliszewski CR, Schooley K, Griffith TS. Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).  J Exp Med. 1999;  190 1155-1161
  • 12 Papewalis C, Jacobs B, Wuttke M, Ullrich E, Baehring T, Fenk R, Willenberg H, Schinner S, Cohnen M, Seissler J, Zacharowski K, Scherbaum WA, Schott M. IFN-alpha skews monocytes into CD56+ expressing dendritic cells with potent functional activities in vitro and in vivo J Immunol.  2008;  180 , in press
  • 13 Mohty M, Vialle-Castellano A, Nunes JA, Isnardon D, Olive D, Gaugler B. IFN-alpha skews monocyte differentiation into toll-like receptor 7-expressing dendritic cells with potent functional activities.  J Immunol. 2003;  171 3385-3393
  • 14 Parlato S, Santini SM, Lapenta C, Di Pucchio T, Logozzi M, Spada M, Giammarioli AM, Malorni W, Fais S, Belardelli F. Expression of CCR-7, MIP-3beta, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities.  Blood. 2001;  98 3022-3029
  • 15 Schott M, Seissler J. Dendritic cell vaccination: new hope for the treatment of metastasized endocrine malignancies.  Trends Endocrinol Metab. 2003;  14 156-162
  • 16 Schott M. Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers.  Endocr Relat Cancer. 2006;  13 779-795
  • 17 Papewalis C, Fassnacht M, Willenberg HS, Domberg J, Fenk R, Rohr UP, Schinner S, Bornstein SR, Scherbaum WA, Schott M. Dendritic cells as potential adjuvant for immunotherapy in adrenocortical carcinoma.  Clin Endocrinol (Oxf). 2006;  65 215-222
  • 18 Banchereau J, Ueno H, Dhodapkar M, Connolly J, Finholt JP, Klechevsky E, Blanck JP, Johnston DA, Palucka AK, Fay J. Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.  J Immunother. 2005;  28 505-516

Correspondence

M. SchottMD 

Department of Endocrinology

Diabetes and Rheumatology

University Hospital Duesseldorf

Moorenstr. 5

40225 Duesseldorf

Germany

Phone: +49/211/811 78 10

Fax: +49/211/811 78 60

Email: matthias.schott@uni-duesseldorf.de

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