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Identification and visualization of CD8+ T cell mediated IFN-? signaling in target cells during an antiviral immune response in the brain.


ABSTRACT: CD8(+) T cells infiltrate the brain during an anti-viral immune response. Within the brain CD8(+) T cells recognize cells expressing target antigens, become activated, and secrete IFN?. However, there are no methods to recognize individual cells that respond to IFN?. Using a model that studies the effects of the systemic anti-adenoviral immune response upon brain cells infected with an adenoviral vector in mice, we describe a method that identifies individual cells that respond to IFN?. To identify individual mouse brain cells that respond to IFN? we constructed a series of adenoviral vectors that contain a transcriptional response element that is selectively activated by IFN? signaling, the gamma-activated site (GAS) promoter element; the GAS element drives expression of a transgene, Cre recombinase (Ad-GAS-Cre). Upon binding of IFN? to its receptor, the intracellular signaling cascade activates the GAS promoter, which drives expression of the transgene Cre recombinase. We demonstrate that upon activation of a systemic immune response against adenovirus, CD8(+) T cells infiltrate the brain, interact with target cells, and cause an increase in the number of cells expressing Cre recombinase. This method can be used to identify, study, and eventually determine the long term fate of infected brain cells that are specifically targeted by IFN?. The significance of this method is that it will allow to characterize the networks in the brain that respond to the specific secretion of IFN? by anti-viral CD8(+) T cells that infiltrate the brain. This will allow novel insights into the cellular and molecular responses underlying brain immune responses.

PROVIDER: S-EPMC3163574 | BioStudies |

REPOSITORIES: biostudies

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