HUMAN MICROGLIAL CELLS HAVE PHENOTYPIC AND FUNCTIONAL-CHARACTERISTICSIN COMMON WITH BOTH MACROPHAGES AND DENDRITIC ANTIGEN-PRESENTING CELLS

Resting microglia comprise up to 13% of the cells in human central ner vous system (CNS) white matter, Their large number and dendritic morph ology make them ideally suited to survey the CNS for noxious stimuli. Upon activation microglia gradually lose dendritic processes and trans form into typical phagocytic macrophages, Microglia have been implicat ed as the main antigen presenting cell within the CNS, and appear to b e of central importance as effecters and regulators of demyelination. To further characterize the capacity for immune reactivity within the human CNS, we have studied several characteristics of microglia, both in situ and in vitro. We find that human microglia have ultrastructura l, phenotypic (CD11c, CD68, acid phosphatase), and functional (FcR and CR mediated phagocytosis) properties typical for cells of the monocyt e lineage. Our data indicate that microglia also have properties in co mmon with dendritic antigen-presenting cells. Electron microscopy stud ies show extended dendritic cell processes on cultured microglia, and microglia are, like dendritic cells, negative for the monocyte markers nonspecific esterase, endogenous peroxidase, CD14, and RFD7. Microgli a constitutively express HLA-DR in situ, and express the dendritic cel l marker RFD1 upon activation, Coculturing of microglia with CD4(+) T cells results in clustering of T cells around microglia and initiation of a mixed lymphocyte reaction, both distinguishing features of dendr itic cells. These functional properties of microglia may be of importa nce for the maintenance of an immunologic response in the CNS, an orga n where dendritic cells, in contrast to other organs, have not previou sly been identified.