Antigen presentation function of brain-derived dendriform cells depends on astrocyte help

Hans Georg Fischer, Anja K. Bielinsky

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

In mouse brain primary culture, supplementation with granulocyte macrophage colony-stimulating factor (GM-CSF) induces development of dendriform cells emerging on the astroglia monolayer. As revealed by flow cytofluorimetric analysis, > 70% of isolated cells are CD11c+ and express the dendritic cell (DC) marker 33D1. Additional expression of F4/80 and CD11b suggests a myeloid origin of these cells. The lymphoid DC marker CD8α is lacking while DEC-205 has been detected on ~ 10% of the cells. When freshly isolated, such brain-derived DC-like cells are excellent antigen-presenting cells (APC) but their functional capability is lost during subculture with GM-CSF. In contrast, their antigen presentation function remains stable in the presence of GM-CSF plus astrocytes or astrocyte-conditioned medium. The responsible astrocytic activity co-fractionates with macrophage colony-stimulating factor (M-CSF). Neutralization of the activity with anti-M-CSF antibody and substitution with recombinant M-CSF provide evidence that, in addition to GM-CSF, M-CSF is required to preserve the functional capability of these brain-derived APC. Responsiveness of the isolated cells to M-CSF is substantiated by the expression of c-fms/M-CSF receptor gene. Consistently, GM-CSF proves stimulatory for astrocytes by up-regulating their secretion of M-CSF. Furthermore, depletion or blocking of endogenous M-CSF in primary brain cell culture prevents the development of functionally active APC regardless of exogenous GM-CSF. In sum, these findings ascribe an immature DC phenotype to GM-CSF-grown myeloid brain cells and indicate a role for astrocytic M-CSF in maintaining their antigen presentation function.

Original languageEnglish (US)
Pages (from-to)1265-1273
Number of pages9
JournalInternational Immunology
Volume11
Issue number8
DOIs
StatePublished - Aug 9 1999

Keywords

  • Antigen presentation
  • Astrocytes
  • Brain
  • Dendritic cells
  • Macrophage colony-stimulating factor

Fingerprint Dive into the research topics of 'Antigen presentation function of brain-derived dendriform cells depends on astrocyte help'. Together they form a unique fingerprint.

Cite this