Non-neural-specific T lymphocytes can orchestrate inflammatory peripheral neuropathy

Abstract

Neural-specific T lymphocytes are held to play a pathological role in inflammatory peripheral nerve disorders such as the Guillain-Barré 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 2 x 10(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 (5 x 10(6)) induced severe Wallerian degeneration and nerve conduction failure in ovalbumin injected nerves. Fewer T cells (5 x 10(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.

The Role of Apolipoprotein E in Guillain-Barré Syndrome and Experimental Autoimmune Neuritis

“…The blood nerve barrier (BNB) breakdown and autoreactive T cell penetrating BNB are crucial in the initiation of GBS [130, 131]. Data from animal experiments suggested that BNB dysfunction resulting from apoE deficiency might lead to more susceptibility to GBS, and exacerbate clinical GBS [132, 133].…”

Sural nerve T-cell receptor Vβ gene utilization in chronic inflammatory demyelinating polyneuropathy and vasculitic neuropathy

“…[31][32][33] Another function of nonspecific T cells may be to increase the blood-nerve barrier permeability and recruit macrophages, as has been hypothesized in experimental model of inflammatory neuropathy in Lewis rats. 34,35 Local accumulation of high numbers of non-neural T cells induced severe axonal degeneration and conduction failure, while lower numbers induced conduction block and mild demyelination. Neural damage could be induced by soluble proinflammatory mediators released by T cells and macrophages which could damage susceptible Schwann cells first, and then axons.…”

Advances in understanding and treatment of immune‐mediated disorders of the peripheral nervous system

“…The injection of CD4 ϩ T-lymphocytes reactive to the non-neural antigen ovalbumin induced mononuclear inflammatory infiltrates in the tibial nerve of Lewis rats that had received a previous intraneural injection of ovalbumin. 90,205 Clinically and morphologically, these animals resembled those with P2-induced EAN. The observation that activated T-cells of non-neural specificity prompt the breakdown of the blood-nerve barrier and produce clinical symptoms similar to human GBS underlines the pathogenetic relevance of the concept of molecular mimicry, as discussed in what follows.…”