Brain Trm die rapidly on isolation from the tissue and fail to undergo recall expansion after adoptive transfer into the bloodstream of antigen-challenged recipients. 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. Antigen persistence is not a prerequisite for T-cell retention, as suggested by the failure to detect viral genomes in the T-cell clusters. After clearance of virus, CD8 + T cells persist in tight clusters, presumably at prior infection hot spots. Brain Trm selectively express the integrin CD103, the expression of which is dependent on antigen recognition within the tissue. These cells survive without replenishment from the circulation and are referred to as resident memory T cells (Trm). However, viral infection of the brain results in the infiltration and long-term persistence of pathogen-specific CD8 + T cells. The brain is not routinely surveyed by lymphocytes and is defined as an immuno-privileged site.
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