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 development of central nervous system inflammation. This may result in full T cell activation, a partial state of activation, anergy or apoptosis of the 'responding' T cell. Here, we demonstrate that neonatal rodent microglia not only fail to initiate a mixed lymphocyte reaction (MLR), but suppress background T cell proliferation. Even after activation with gamma-IFN or following phagocytosis, microglia remain unable to support a MLR. By contrast, gamma-IFN-activated microglia are able to activate memory T cells in a recall assay resulting in cytokine (gamma-IFN) release and modest T cell proliferation. Although the stimulation index is small, functional relevance is demonstrated. Supernatants from the recall assay stimulate gamma-IFN-dependent activation of a STAT (signal transducer and activator of transcription) factor within resting microglia. This demonstrates that memory T cells not only receive sufficient stimulation from the gamma-IFN-activated microglia to proliferate and produce cytokines, but that there is also a reciprocal stimulation of resting microglia. Importantly, this provides evidence that activated microglia have the potential to propagate immune responses in the central nervous system, but are unlikely to initiate a primary response.
Hall
G L
GL
University of Cambridge Neurology Unit, Addenbrooke's Hospital, UK.
Girdlestone
J
J
Compston
D A
DA
Wing
M G
MG
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017628:Microglia / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D015345:Oligonucleotide Probes; D010587:Phagocytosis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D000906:Antibodies; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015345:Oligonucleotide Probes; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma