Dendritic cells generated in the presence of GM-CSF plus IL-15 prime potent CD8+ Tc1 responses in vivo

Bali Pulendran, Stephanie Dillon, Chryshanthi Joseph, Tyler Curiel, Jacques Banchereau, Mansour Mohamadzadeh

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Dendritic cells (DC) comprise a system of professional antigen-presenting cells, which induce the stimulation of very rare antigen-specific naive T cells. DC progenitors can be stimulated to differentiate into immature DC by various growth factors, including GM-CSF and IL-4. Here we show that IL-15, in combination with GM-CSF is a growth factor for murine DC. Murine bone marrow cells, depleted of T cells, B cells, I-A+ cells and Gr-1+ granulocytes, and cultured in the presence of GM-CSF plus IL-15 (IL-15 DC), yielded DC expressing high levels of CD11c and MHC class II molecules, as well as CD11b. These cells expressed significant levels of CD40, CD80 and CD86, and could stimulate allogeneic CD4+ T cells efficiently. Interestingly, IL-15 DC were far superior to DC generated with GM-CSF plus IL-4 in stimulating allogeneic CD8+ T cells in vitro. Consistent with this, IL-15 DC induced much more potent antigen-specific CD8+ T cell responses with high levels of Th1 cytokines in vivo, compared to DC generated with GM-CSF plus IL-4, or with GM-CSF plus TGF-β, or with GM-CSF alone. Together, these data suggest that IL-15 promotes the development of DC, which induce potent Th1 and Tc1 responses in vivo. This suggests potential roles for these IL-15 DC cells in the immunotherapy of tumors and infectious diseases.

Original languageEnglish (US)
Pages (from-to)66-73
Number of pages8
JournalEuropean Journal of Immunology
Volume34
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • CD8 T cells
  • Cytokines
  • Dendritic cells
  • Th1
  • Th2 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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