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The Journal of Neuroscience, January 18, 2006, 26(3):731-741; doi:10.1523/JNEUROSCI.3502-05.2006
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Neurobiology of Disease
Traumatic Injury and the Presence of Antigen Differentially Contribute to T-Cell Recruitment in the CNS
Changying Ling,1 Matyas Sandor,1 M. Suresh,2 andZsuzsa Fabry1 1Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison Medical School, and 2Department of Pathological Science, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, Wisconsin 53706
T-cell recruitment into the brain is critical in inflammatory and autoimmune diseases of the CNS. We use intracerebral antigen microinjection and tetramer technology to track antigen-specific CD8+ T-cells in the CNS and to clarify the contribution of antigen deposition or traumatic injury to the accumulation of T-cells in the brain. We demonstrate that, after intracerebral microinjection of ovalbumin, ovalbumin-specific CD8+ T-cells expand systemically and then migrate into the brain where they complete additional proliferation cycles. T-cells in the brain are activated and respond to in vitro secondary antigen challenge. CD8+ T-cells accumulate and persist in sites of antigen in the brain without replenishment from the periphery. Persistent survival of CD8+ T-cells at sites of cognate antigen is significantly reduced by blocking CD154 molecules. A small traumatic injury itself does not lead to recruitment of CD8+ T-cells into the brain but attracts activated antigen-specific CD8+ T-cells from cognate antigen injection sites. This process is presumably antigen independent and cannot be inhibited by blocking CD154 molecules. These data show that activated antigen-specific CD8+ T-cells accumulate in the CNS at both cognate antigen-containing and traumatic injury sites after intracerebral antigen delivery. The accumulation of activated antigen-specific T-cells at traumatic injury sites, in addition to antigen-containing areas, could amplify local inflammatory processes in the CNS. Combination therapies in neuroinflammatory diseases to block both of these processes should be considered.
Key words: antigen specificity; CD8+ T-cell homing; traumatic brain injury; neuroimmunology; ovalbumin antigen; intracerebral injection
Received Aug 18, 2005; revised November 8, 2005; accepted November 14, 2005.
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