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 lymphocy tes induce the production of inflammatory cytokines. Since this interaction can occur in a non-antigen-dependent manner, it is relevant to a variety o f CNS diseases where activated T cells, regardless of specificities, come i nto contact with microglia; these disorders include multiple sclerosis, tra uma, stroke and Alzheimer's disease. A model cell line would facilitate stu dies 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 similariti es to microglia in its interaction with activated T lymphocytes, in that th e production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-I O and IL-12 is induced. Morphological features and mechanisms of cytokine p roduction resemble those observed in microglia-T cell co-cultures since CTL A-4 and CD40-CD40L blockades reduce TNF-cr and IL-10 levels, while anti-CD2 3 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 cell s. (C) 2001 Elsevier Science B.V. All rights reserved.