NON-NEURAL-SPECIFIC T-LYMPHOCYTES CAN ORCHESTRATE INFLAMMATORY PERIPHERAL NEUROPATHY

Neural-specific T lymphocytes are held to play a pathological role in inflammatory peripheral nerve disorders such as the Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Here, non-neural-specific T-cell-mediated inflammation was studied in peripheral nerves in Lewis rats by systemic transfer of ovalbumin-specific activated T cells followed by intraneural injection of ovalbumin. Rapid endoneurial perivenular infiltration of alpha beta T cells and ED1(+) macrophages occurred with ovalbumin injection following transfer of 2X10(6) T cells. This cellular infiltration and accumulation produced marked increases in blood-nerve barrier (BNB) permeability. In contrast, control casein injections produced neither significant cell accumulation nor BNB permeability changes. Transfer of a higher number of T cells (5X10(6)) induced severe Wallerian degeneration and nerve conduction failure in ovalbumin injected nerves. Fewer T cells (5X10(5)) induced conduction block and mild demyelination which were markedly augmented by systemic cotransfer of anti-myelin immunoglobulin. This study demonstrates that activated T cells of non-neural specificity can accumulate in peripheral nerve, produce dramatic changes in BNB permeability and with intravenous anti-myelin antibody orchestrate primary demyelination or axonal degeneration in a dose-dependent fashion.