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Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence

Linda M. Wakim, Amanda Woodward-Davis, Michael J. Bevan and Rafi Ahmed
Proceedings of the National Academy of Sciences of the United States of America
Vol. 107, No. 42 (October 19, 2010), pp. 17872-17879
Stable URL: http://www.jstor.org/stable/25748407
Page Count: 8
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Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence
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Abstract

The brain is not routinely surveyed by lymphocytes and is defined as an immuno-privileged site. However, viral infection of the brain results in the infiltration and long-term persistence of pathogen-specific CD8⁺ T cells. These cells survive without replenishment from the circulation and are referred to as resident memory T cells (Trm). Brain Trm selectively express the integrin CD103, the expression of which is dependent on antigen recognition within the tissue. After clearance of virus, CD8⁺ T cells persist in tight clusters, presumably at prior infection hot spots. Antigen persistence is not a prerequisite for T-cell retention, as suggested by the failure to detect viral genomes in the T-cell clusters. Furthermore, we show that an intracranial dendritic cell immunization regimen, which allows the transient introduction of antigen, also results in the generation of memory T cells that persist long term in the brain. Brain Trm die rapidly on isolation from the tissue and fail to undergo recall expansion after adoptive transfer into the blood-stream of antigen-challenged recipients. These ex vivo defects imply a dependency on the local milieu for function and survival. Cumulatively, this work shows that Trm are a specialized population of memory T cells that can be deposited in tissues previously thought to be beyond routine immune surveillance.

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