INTRANEURAL ACTIVATED T-CELLS CAUSE FOCAL BREAKDOWN OF THE BLOOD-NERVE BARRIER

Experiments were conducted to investigate the effect of activated T ce lls on the blood-nerve barrier (BNB) in experimental allergic neuritis (EAN). T cells reactive to the P-2 component of myelin (P-2 T cells) and known to cause EAN were injected into the sciatic nerve of Lewis r ats. Animals were then given daily intraperitonenal (i.p.) injections of serum with known demyelinating activity (rabbit EAN serum) or contr ol serum. Serial nerve conduction studies across the injected segment were performed and nerves were removed at various stages for histology . Focal conduction block and perivascular demyelination were evident i n T cell injected nerves of animals treated with EAN serum. In animals treated with control serum no conduction block was seen and only peri vascular infiltrates without demyelination were present. Similar resul ts were obtained with T cells reactive to non-neural antigens, althoug h the effect was less marked. Systemically administered rabbit immunog lobulin (Ig) was demonstrated within the endoneurium of P-2 T cell inj ected nerves by immunofluorescence and the endoneurial blood vessels s howed increased permeability to circulating horseradish peroxidase (HR P). These findings demonstrate that activated T cells cause focal brea kdown of the BNB, allowing circulating antimyelin antibody to enter th e endoneurium with consequent focal demyelination. P-2 reactive EAN pr oducing T cells do not cause significant demyelination when injected i ntraneurally (i.n.) in the absence of circulating antimyelin antibody. Intraneural injection of tumour necrosis factor alpha (TNF-alpha) yie lded similar results, causing conduction block and perivascular demyel ination in the presence of circulating antimyelin antibody but not in control serum treated animals.