Astrocytic Factors Deactivate Antigen Presenting Cells that Invade the Central Nervous System

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Abstract
We hypothesized that CNS tissue has the potential to deactivate invading monocytes/macrophages in order to maintain the immune privilege of the brain, and furthermore, that astrocytes are the cells that initiate monocyte/macrophage deactivation. To test this hypothesis, fluorescent prelabeled rat spleen macrophages with typical amoeboid morphology were transferred into organotypic hip‐pocampal slice cultures (OHSCs), where they gradually developed a ramified morphology similar to the appearance of resting microglial cells. This morphological transformation also occurred if macrophages or monocytes were co‐cultured with mixed glial cultures or with astrocytoma cells, and ramification was accompanied by reduced expression of adhesion molecules leukocyte function antigen (LFA)‐1, intercellular adhesion molecule (ICAM)‐1, and major histocompatibility complex (MHC)‐class‐II molecules. Moreover, treatment of macrophages with astrocyte culture supernatant effectively down‐regulated the LPS‐induced expression of adhesion‐ and MHC‐class‐II‐molecules. Astrocyte supernatant‐induced inhibition of adhesion and MHC‐class‐II‐molecule expression was mimicked by transforming growth factor (TGF)‐β1, furthermore, this inhibitory effect was diminished by simultaneous treatment with neutralizing anti‐TGF‐β‐antibodies. In conclusion, our results suggest that astrocyte‐derived, soluble factors that are present in the CNS microenvironment deactivate invading macrophages, thus contributing to the maintenance of CNS immune‐privilege following impairment of blood‐brain‐barrier (BBB) integrity.