Recall antigen presentation by gamma-interferon-activated microglia results in T cell activation and propagation of the immune response

The interaction between microglia and T cells is important in the developme nt of central nervous system inflammation. This may result in full T cell a ctivation, a partial state of activation, anergy or apaptosis of the 'respo nding' T cell. Here, we demonstrate that neonatal rodent microglia not only fail to initiate a mixed lymphocyte reaction (MLR), but suppress backgroun d T cell proliferation. Even after activation with gamma-IFN or following p hagocytosis, microglia remain unable to support a MLR. By contrast, gamma-I FN-activated microglia are able to activate memory T cells in a recall assa y resulting in cytokine (gamma-IFN) release and modest T cell proliferation . Although the stimulation index is small, functional relevance is demonstr ated. Supernatants from the recall assay stimulate gamma-IFN-dependent acti vation of a STAT (signal transducer and activator of transcription) factor within resting microglia. This demonstrates that memory T cells not only re ceive sufficient stimulation from the gamma-IFN-activated microglia to prol iferate and produce cytokines, but that there is also a reciprocal stimulat ion of resting microglia. importantly, this provides evidence that activate d microglia have the potential to propagate immune responses in the central nervous system, but are unlikely to initiate a primary response. (C) 1999 Elsevier Science B.V. All rights reserved.