International Immunology, Vol. 11, No. 8, 1265-1274,
August 1999
© 1999 Japanese Society for Immunology
Antigen presentation function of brain-derived dendriform cells depends on astrocyte help
Institute for Medical Microbiology and Virology, Heinrich-Heine-University, Universitätsstrasse 1, Geb. 22.21, 40225 Düsseldorf, Germany
Correspondence to: H.-G. Fischer
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 CD8
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.
Keywords: antigen presentation, astrocytes, brain, dendritic cells, macrophage colony-stimulating factor
1 Present address: Department of Molecular Biology, Cell Biology and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA
Transmitting editor: A. McMichael
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