ENRICHED IMMUNE-ENVIRONMENT OF BLOOD-BRAIN-BARRIER DEFICIENT AREAS OFNORMAL ADULT-RATS

The circumventricular organs (CVOs) in the brain are without a blood-b rain barrier (BBB) and as such directly exposed to blood plasma consti tuents and blood-borne pathogens. In light of previous studies showing discrepancies regarding the immunocompetence of these organs, we init iated the present study to provide a comprehensive immunohistochemical analysis of the cellular expression of immune-associated antigens wit hin the pineal gland, area postrema and the subfornical organ. In all CVOs, subpopulations of cells morphologically similar to complement re ceptor type 3 immunoreactive microglial/macrophage cells expressed maj or histocompatibility complex (MHC) class II antigen, leucocyte common antigen (LCA/CD45), as well as CD4 and ED1 antigen. Based on morpholo gical criteria the MHC class II antigen expressing cells could be grou ped into a major population of classical parenchymal and perivascular ramified microglial cells and a minor population presenting itself as scattered or small groups of rounded macrophage-like cells. CD4 and ED 1 antigen were expressed by both cell types. CD45 was preferentially e xpressed by macrophage-like cells. MHC class I antigen was expressed b y the vascular endothelium in both BBB-protected and BBB-deficient are as and was additionally present as a lattice-like network throughout t he BBB-deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of the brain besides being constantly surveyed by blood -borne macrophages, possess an intrinsic immune surveillance system ba sed on resting and activated microglial cells, which may function as a non-endothelial, cellular barrier against blood-borne pathogens.