Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses

Cancer Immunol Immunother. 2005 Aug;54(8):769-80. doi: 10.1007/s00262-004-0637-2. Epub 2005 Jan 13.

Abstract

Dendritic cells (DC) are candidates for antigen-presenting cells that present exogenous antigen on MHC class I molecules to cytotoxic T lymphocytes (CTL), a process referred to as cross-priming. We triggered interleukin (IL)-12 release from DC, which was limited to the first day after maturation induction, by a combination of lipopolysaccharide (LPS) and interferon (IFN)-gamma. To stimulate T lymphocytes, we used soluble protein derived from lysis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) or ovalbumin loaded onto DC. Co-culture was initiated 2-6 or 48 h after maturation corresponding to "semi-mature" actively IL-12-secreting type 1 DC (sm-DC1) or a "fully mature" DC1 that had lost the ability to release IL-12 (fm-DC1), respectively. IL-12-secreting sm-DC1 but not fm-DC1 efficiently triggered cytolytic activity in autologous T lymphocytes. The combination of IL-1beta, IL-6, TNF-alpha, and prostaglandin E2 generated type 2 DC that did not secrete IL-12 (DC2) and could not prime T-cell cytolytic activity. However, supplementation of cultures using DC2 with IL-12 resulted in CTL activity while the presence of anti-IL-12 monoclonal antibodies in cultures using IL-12 secreting sm-DC1 suppressed CTL activity. Thus, actively IL-12-secreting sm-DC1 are necessary and sufficient for the antigen-specific expansion of CTL in response to exogenously provided soluble antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Antigen Presentation / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Culture Techniques
  • Cell Death
  • Cross-Priming*
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Herpesvirus 4, Human / immunology
  • Humans
  • Interleukin-12 / metabolism*
  • Ovalbumin / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Interleukin-12
  • Ovalbumin