GMCSF in the absence of other cytokines sustains human dendritic cell precursors with T cell regulatory activity and capacity to differentiate into functional dendritic cells

Sriram Chitta, Laura Santambrogio, Lawrence J. Stern

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Dendritic cell precursors, from human peripheral blood, express epitopes reactive with monoclonal antibodies specific for the empty conformation of HLA-DR1. Expression is substantially up-regulated during GMCSF-induced differentiation to immature dendritic cells, but is strongly down-regulated by IL-4. In the conventional protocol for in vitro generation of human dendritic cells from monocyte precursors, both GMCSF and IL-4 are used together, with IL-4 thought to have an effect on preventing macrophage outgrowth but not substantially altering the dendritic cell maturation pathway, whereas conventional protocols for generation of murine dendritic cells use GMCSF alone. We characterized human monocytes cultured in the presence of GMCSF and in the absence of IL-4, and found that the resultant cultures are stable for long periods in vitro, and have T cell stimulatory and immunodulatory activity characteristic of immature dendritic cells. Their response to maturation stimuli is weak in the absence of IL-4 but these cells retain the ability to differentiate into fully functional mature dendritic cells upon IL-4 treatment. We suggest that these cells may provide a useful model to investigate tolerogenic function as a developmental feature of DC and to understand molecular events involved in IL-4 priming for maturation.

Original languageEnglish (US)
Pages (from-to)41-54
Number of pages14
JournalImmunology Letters
Volume116
Issue number1
DOIs
StatePublished - Feb 15 2008

Keywords

  • Antigen presentation
  • GMCSF
  • MHC molecules
  • Maturation
  • Monocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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