The Cerebral Perivascular Cells

摘要: This monograph reviews the literature and presents experimental data on intracerebral presentation of antigen(s) to immune system as a consequence neuronal cell death. "Which cells are antigen presenting (APC) brain?" is main question this book. The surveillance CNS occurs through specialized resident cells, which present (auto)antigen(s) thus initiate an (auto)immune response. There four established prerequisites necessary identify APC brain. First, must be capable phagocytose dead neurons. Second, in order recognized by T lymphocytes, these neuronophages express Major Histocompatibility Complex (MHC) II glycoproteins their surface. Third, (auto)antigen, MHC class II-positive also able contact lymphocytes. Fourth, exert stimulatory effect should produce cytokine interleukin-1 beta (IL-128 Mb). Three tools were used characterize lesion model was employed that yields slowly progressing loss without disruption blood-brain barrier. consisted resection 10 mm facial nerve, caused occurring death so one year after amount neurons about 44% control value. labeled vivo situ via phagocytosis permanent fluorescent marker Fluoro-Gold (FG) from decaying pre-loaded motoneurons. FG-labeled immunocytochemically characterized with new method "immunoquenching fluorescence". Sections brainstem containing FG-labeled, i.e. fluorescent, incubated variety primary antibodies, followed avidin-HRP DAB-nickel dark brown reaction product for bright-field microscopy. In mode DAB selectively quenches fluorescence all immunopositive only those do not bind antibody remain fluorescent. Combining FG-labeling immunoquenching, population small round discovered, localized immediate vicinity motoneurons long neuronofugal migration microglia. As quenched triple immunostaining anti-neuronal-specific enolase, anti-GFAP OX-42 (quenching neurons, astroglia, microglia), they seem represent new, immunologically unidentified neuronophage. Following immunostaining, broad panel antibodies tested stain, quench fluorescence, immunotype enigmatic phagocytes. Only monoclonal ED2, classical perivascular specifically stained neuronophages. Although basal lamina cerebral vasculature, confused pericytes, perform phagocytosis. contrast, macrophages-ED2 recognizes macrophage membrane antigen. addition, injury subset starts synthesize IL-1 beta. Hence seems possess complete machinery required presentation: They macrophages, upregulate molecules beta, due anatomical location, have access circulating What still lacking, however, direct proof neuronophagia. Our experiments provided proof. (ABSTRACT TRUNCATED)