Cytokine production consequent to T cell--microglia interaction: the PMA/IFN gamma-treated U937 cells display similarities to human microglia.
Cognate interactions between human adult microglia and activated T lymphocytes induce the production of inflammatory cytokines. Since this interaction can occur in a non-antigen-dependent manner, it is relevant to a variety of CNS diseases where activated T cells, regardless of specificities, come into contact with microglia; these disorders include multiple sclerosis, trauma, stroke and Alzheimer's disease. A model cell line would facilitate studies of the engagement between T cells and human adult microglia, since the latter are difficult to obtain in substantial quantity or frequency. This study shows that the PMA/IFN gamma-treated U937 cell line shows similarities to microglia in its interaction with activated T lymphocytes, in that the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10 and IL-12 is induced. Morphological features and mechanisms of cytokine production resemble those observed in microglia--T cell co-cultures since CTLA-4 and CD40--CD40L blockades reduce TNF-alpha and IL-10 levels, while anti-CD23 inhibits IL-10 only in U937--T cell interactions. We propose that PMA/IFN gamma-treated U937 cells can serve as a model of human adult microglia to study cytokine generation in response to interactions with activated T cells.
Departments of Oncology and Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alta, Canada T2N 4N1.
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Chabot
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Charlet
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Wilson
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Yong
D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D018122:B7-1 Antigen / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000276:immunology; D002493:Central Nervous System Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D017455:Receptors, IgE / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D020298:U937 Cells
D000906:Antibodies; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D002273:Carcinogens; D016207:Cytokines; D008562:Membrane Glycoproteins; D017455:Receptors, IgE; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate