Antigen presentation and tumor cytotoxicity by interferon‐γ‐treated microglial cells

Abstract

In this study microglial cells isolated from brain cell cultures of newborn mice were characterized and investigated for morphology, their responses to growth factors and their functional properties. The microglial cells were phagocytic, contained nonspecific esterase activity and expressed Fc (IgG1/2b) and type-3 complement receptors. Scanning electron microscopy revealed that in analogy to brain tissue two types of microglial cells are present in the cultures: the ameboid and the ramified type which both display similar appearance by transmission electron microscopy. Interleukin 3 and the granulocyte-macrophage colony-stimulating factor were potent growth factors for the cultured microglial cells. The cells were negative for class II antigens (Ia) of the major histocompatibility antigen complex. However, upon treatment with interferon-gamma (IFN-gamma) microglial cells became Ia+ and functioned as antigen-presenting cells when tested on ovalbumin-specific Ia-restricted helper T cells. Furthermore, microglial cells exposed to IFN-gamma and endotoxin developed tumor cell cytotoxicity and produced tumor necrosis factor alpha. Taken together, microglial cells share the characteristics of cells of the macrophage lineage.

Site‐specific anti‐tumor immunity: Differences in DC function, TGF‐β production and numbers of intratumoral Foxp3+ Treg

“…Glioma cells work poorly as APC due to a low expression of MHC molecules and a lack of co-stimulatory molecules, which are needed to reactivate the primed T cells [37]. Microglia, which have been described to function as APC in vitro [38], are unable to present glioma cell antigens to cytotoxic T lymphocytes [39]. Moreover, using congenic BM chimeras, we did not see any involvement of microglia in the anti-tumor response.…”

Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

“…In chronic active MS lesions, the presence of large amounts of TNF is associated with high expression of ICAM-1 and VCAM-1 on blood vessels [24]. Astrocytes, microglia and perivascular macrophages are potential sources of TNF [25,26], whose release may be triggered by exogenous stimuli such as viral infection [27] or by the action of other cytokines secreted by immunocompetent cells [9]. Our finding that TNF-was highly efficient at increasing the adhesiveness of cultured endothelial cells for MS lymphocytes adds credence to the view that this cytokine is one of the main inflammatory factors that promote lymphocyte extravasation across the BBB in MS.…”

Microglia at brain stab wounds express connexin 43 andin vitroform functional gap junctions after treatment with interferon-γ and tumor necrosis factor-α

“…About 95% of the cells were positive for glial fibrillary acidic protein, indicating that cultures were highly enriched in astrocytes; presumably most of the remaining 5% were microglia. Because microglia proliferate in astrocyte-conditioned medium (24), feeding of confluent cultures was stopped for the following 12-14 days. Cultures were then rigorously agitated for 30 min in an orbital shaker (Lab-Line Instruments) at 150 rpm and 37°C to detach cells adhering to the astrocyte monolayer.…”