ACTIVATED T-CELLS OF NONNEURAL SPECIFICITY OPEN THE BLOOD-NERVE BARRIER TO CIRCULATING ANTIBODY

Recent studies from our laboratory and by other investigators have sho wn that autoreactive CD4(+) cells specific for peripheral. nerve P-2 p rotein have a powerful effect on blood-nerve barrier permeability. In this study we injected CD4(+) T cells reactive to a nonneural antigen (ovalbumin) systemically and achieved their accumulation in the tibial nerve of Lewis rats by previous intraneural injection of ovalbumin. S elected rats were given systemic demyelinating antibody (antigalactoce rebroside) to provide an indicator of changes in the permeability of t he blood-nerve barrier, and the animals were monitored by sequential n europhysiological studies and histology. Circulating ovalbumin-specifi c T cells accumulated at sites of intraneural. ovalbumin injection wit hout inducing demyelination in control animals. In rats with circulati ng galactocerebroside antibodies, local conduction block and demyelina tion were seen in the region of T-cell accumulation. Electron microsco py demonstrated dissolution of some tight junctions between endothelia l cells in areas of T-cell accumulation, and T cells traversing the en dothelium between endothelial cells and through their cytoplasm. Endot helial cell damage was evident in these areas. This study demonstrates breakdown of the blood-nerve barrier by activated T cells, even of no nneural specificity, allowing the development of focal conduction bloc k and demyelination in the presence of circulating antimyelin antibodi es.