Activated non-neural specific T cells open the blood-brain barrier to circulating antibodies

Previous studies have shown that activated T cells can successfully cross e ndothelial barriers and will accumulate in tissue which contains their spec ific antigen. Myelin specific T cells (e.g. myelin basic protein specific) are recognized to play an important role in the induction of experimental a utoimmune demyelinating disease of the CNS and have been shown to induce bl ood-brain barrier breakdown effectively. In this study we injected T cells reactive to a non-neural antigen (ovalbumin) systemically into Lewis rats a nd caused them to accumulate in the thoracic dorsal column by a prior injec tion of ovalbumin. Selected rats were given systemic demyelinating antibody , antimyelin oligodendrocyte antibody (anti-MOG antibody), to provide evide nce of permeability changes to the blood-brain barrier. These animals were compared with control rats given systemic anti-P-0 monoclonal antibody and to other rats given a direct micro-injection (3 mu l) of anti-MOG antibody into the thoracic dorsal column. All animals were monitored by serial neuro physiological studies and by histological examination. Direct anti-MOG anti body injection produced a focal block in conduction at the injection site a nd a large circumscribed area of primary demyelination with axonal preserva tion within the dorsal column. An even more profound conduction block and m ore extensive plaque-like region of demyelination were seen in animals give n antigen, activated T cells and systemic antibody. However, animals given antigen and T cells without relevant antibody did not show conduction impai rment or demyelination, except when very large numbers of T cells were give n; such rats developed severe irreversible axonal damage. This study demons trates the blood-brain barrier is disrupted by activated T cells of non-neu ral specificity and allows large plaque-like regions of demyelination to fo rm in the presence of circulating antimyelin antibody. The relevance of thi s finding to multiple sclerosis is discussed.