Intracerebral granulocyte‐macrophage colony‐stimulating factor induces functionally competent dendritic cells in the mouse brain

Abstract Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is a hematopoietic growth factor and a proinflammatory cytokine. While GM‐CSF is lacking in normal brain tissue, it is expressed under pathological conditions and correlates with the presence of dendritic cells (DC). However, the role of GM‐CSF for the onset of immune responses in the brain is still unclear. To analyze the role of GM‐CSF for the induction and functional activity of immune cells in the brain, we performed chronic intracerebroventricular administration of GM‐CSF to the brains of adult mice. After GM‐CSF administration, intracerebral leukocytes (ICL) were characterized by means of flow cytometry, immunohistochemistry, and an ex vivo functional assay. GM‐CSF treatment significantly increased the number of leukocytes expressing high levels of CD45, indicative of peripheral, blood‐derived cells. The infiltrating cells were preferentially DC of the myeloid lineage (CD45 high CD11c + CD11b + ) with an activated phenotype characterized by upregulated expression of MHCII and the costimulatory ligand CD80. Furthermore, DC from GM‐CSF treated mice were fully competent to activate naive allogeneic T cells in a mixed leukocyte reaction. In contrast, intracerebroventricular IFN‐γ administration stimulated MHCII expression on cells resembling resident microglia, but did not induce comparable presence of DC. Taken together, intracerebroventricular GM‐CSF treatment results in high numbers of DC in the brain. Moreover, these GM‐CSF‐induced DC display an activated phenotype and exhibit the capacity to act as fully competent DC even without a further inflammatory stimulus. © 2009 Wiley‐Liss, Inc.