1 April 2002. The old dogma that the brain and the immune system don't mix is crumbling. We now know that the CNS is not entirely privileged, and that immune cells do invade it under certain conditions. This realization, in part, led to the development of the failed Aβ42 vaccine, which has demonstrated effectively how poorly we still understand the interplay between the CNS and the immune system.
The immune system's role in repairing neurons is also something of a mystery. For example, though T cell infiltration after spinal cord injury is thought to contribute to the healing process, just how this occurs is controversial. Are T cells that recognize CNS antigens essential, or is it the recruitment of non-CNS-reactive cells that is important?
Philip Popovich and colleagues, at Ohio State University of Medicine and Public Health, have addressed this question in a paper in today's Journal of Neuroscience. The authors examined the recovery from spinal cord injury in transgenic mice engineered so that more than 95 percent of their T cells recognize myelin basic protein (MBP), versus wildtype.
The transgenic group showed consistently poorer recovery from spinal cord trauma. They exhibited much greater demyelination, more axon loss, and impaired lumbar reflexes compared to wildtype mice. They also had a much greater complement of pro-inflammatory cytokines in their spinal fluid, including IFN-γ, IL-1β, and TNFα.
"If neuroprotection is realized by inducing an auto-reactive response, it is probably as a result of other inflammatory cells that are recruited to the CNS along with the MBP-reactive cells," said Popovich. The authors also caution that people genetically predisposed to autoimmune diseases of the CNS may be adversely affected by autoreactive vaccine therapies. Interestingly in this regard, early indications are emerging that the encephalitis that grounded the Aβ42 vaccine trial may have resulted from a T-cell response, see IPSEN meeting report.-Tom Fagan.
Jones TB, Basso DM, Sodhi A, Pan JZ, Hart RP, MacCallum RC, Lee S, Whitacre CC, Popovich PG. Pathological central nervous system autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapies. J. Neurosci. April 2002;(22):2690-2700. Abstract