Intraneural activated T cells cause focal breakdown of the blood-nerve barrier.
Experiments were conducted to investigate the effect of activated T cells on the blood-nerve barrier (BNB) in experimental allergic neuritis (EAN). T cells reactive to the P2 component of myelin (P2 T cells) and known to cause EAN were injected into the sciatic nerve of Lewis rats. Animals were then given daily intraperitoneal (i.p.) injections of serum with known demyelinating activity (rabbit EAN serum) or control 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 evidence in T cell injected nerves of animals treated with EAN serum. In animals treated with control serum no conduction block was seen and only perivascular infiltrates without demyelination were present. Similar results were obtained with T cells reactive to non-neural antigens, although the effect was less marked. Systemically administered rabbit immunoglobulin (Ig) was demonstrated within the endoneurium of P2 T cell injected nerves by immunofluorescence and the endoneurial blood vessels showed increased permeability to circulating horseradish peroxidase (HRP). These findings demonstrate that activated T cells cause focal breakdown of the BNB, allowing circulating antimyelin antibody to enter the endoneurium with consequent focal demyelination. P2 reactive EAN producing T cells do not cause significant demyelination when injected intraneurally (i.n.) in the absence of circulating antimyelin antibody. Intraneural injection of tumour necrosis factor alpha (TNF-alpha) yielded similar results, causing conduction block and perivascular demyelination in the presence of circulating antimyelin antibody but not in control serum treated animals.
Spies
J M
JM
Institute of Clinical Neurosciences, University of Sydney, NSW Australia.
Westland
K W
KW
Bonner
J G
JG
Pollard
J D
JD
D000818:Animals; D001790:Blood Physiological Phenomena; D008213:Lymphocyte Activation; D008214:Lymphocytes; D009185:Myelin Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D009186:Myelin Sheath / Q000276:immunology; D009431:Neural Conduction / Q000187:drug effects; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D010539:Permeability; D051381:Rats; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D009185:Myelin Proteins; D014409:Tumor Necrosis Factor-alpha