Pathological CNS @entity792 triggered by traumatic XXXX : implications for autoimmune vaccine therapy.

@entity1 @entity17 @entity19 @entity1961 @entity6441 @entity1566 @entity10927 @entity792 @entity130
Lymphocytes respond to myelin proteins after @entity1566 ( @entity1566 ) and may contribute to post-traumatic secondary degeneration. However, there is increasing evidence that autoreactive T-lymphocytes may also convey neuroprotection and promote functional recovery after CNS injury. To clarify the role of myelin autoreactive lymphocytes after @entity1566 , we performed contusion injuries in the thoracic spinal cord of transgenic (Tg) @entity19 in which >95% of all @entity1961 + T-lymphocytes are reactive with @entity10927 ( @entity10927 ). We observed significantly impaired recovery of locomotor and reflex function in Tg @entity19 compared with non-Tg (nTg) littermates. Measures of functional impairment in Tg @entity19 correlated with significantly less white matter at the injury site, and morphometric comparisons of injured Tg and nTg spinal cords revealed increased rostrocaudal lesion expansion (i.e., secondary degeneration) in Tg @entity19 . Rostrocaudal to the impact site in @entity1566 -nTg @entity19 , @entity17 was restricted to the dorsal funiculus, i.e., axons undergoing @entity6441 . The remaining white matter appeared normal. In contrast, lymphocytes were colocalized with regions of @entity17 and axon loss throughout the white matter of @entity1566 -Tg @entity19 . Impaired neurological function and exacerbated neuropathology in @entity1566 -Tg @entity19 were associated with increased intraspinal production of proinflammatory cytokine mRNA; neurotrophin mRNA was not elevated. These data suggest that endogenous @entity10927 -reactive lymphocytes, activated by traumatic @entity1566 , can contribute to tissue injury and impair functional recovery. Any neuroprotection afforded by myelin-reactive T-cells is likely to be an indirect effect mediated by other non-CNS-reactive lymphocytes. Similar to the Tg @entity19 in this study, a subset of @entity1 that are genetically predisposed to @entity792 of the CNS may be adversely affected by vaccine therapies designed to boost autoreactive lymphocyte responses after CNS @entity130 . Consequently, the safe implementation of such therapies requires that future studies define the mechanisms that control T-cell function within the injured CNS.
