COMPARISON OF PHENOTYPIC AND FUNCTIONAL-PROPERTIES OF IMMEDIATELY EX-VIVO AND CULTURED HUMAN ADULT MICROGLIA

Microglial cells are resident cells of the CNS and are implicated as r egulators and effecters of immune responses which occur within this co mpartment. The precise role of parenchymal microglia remains speculati ve because distinctions between these cells, perivascular ''microglia, '' and blood-derived monocytes/macrophages are not well defined. The c urrent study describes the phenotype and function of microglia immedia tely upon isolation from the non-inflamed adult human CNS and the phen otypic changes which occur in these cells when maintained in tissue cu lture. We find that the characteristic phenotype of immediately ex viv o parenchymal microglia (CD11c(+)/CD45(low)/CD14(-)) corresponds to th at found in situ in the ''normal'' human brain. The phenotype differs from that of perivascular ''microglia'' in situ and PBDM (both CD45(hi )/CD14(++)). The immediately ex vivo microglia express B7-2 and HLA cl ass II molecules and can support alloantigen-induced proliferation by CD4(+) T cells freshly isolated from peripheral blood. Following in vi tro culture, the cells are characterized by a bipolar morphology, cont inued lower levels of CD45 expression compared to PBDM, and slight upr egulation of B7-1 and HLA-DR antigen expression. CD14 becomes expresse d at high levels on the cells, suggesting that CD14 can serve as an ap parent marker of microglia activation which is not based on changes in morphology or APC capacity. Further, treatment of the cells with IFN- gamma and LPS causes further upregulation of HLA-DR and clear expressi on of B7-1 molecules on the surface. The capacity to characterize phen otypic and functional properties of microglia before and after activat ion provides an opportunity to determine means to manipulate the immun e regulatory and effector properties of this cell type. (C) 1996 Wiley -Liss, Inc.