Neural involvement in systemic immune-mediated disorders

TEMPORAL INTERACTIONS BETWEEN T LYMPHOCYTES AND RETINAL ENDOTHELIAL CELL MONOLAYERS IN CO-CULTURE J. Greenwood, V.L. Calder, L Grierson and S.L. L | g h t m a n Department of Clinical Science, Institute of Ophthalmology, Cayton Street, London EC1V 9AT, U.K. The retinal endothelium, which constitutes one aspect of the blc'od-retinal bah'let, is in intimate contact with circulating T cells and is likely to be a prime site of entry during inflammatory eye disease. Using a primary rat .-'etinal microvascular endothelial cell (EC) culture we have investigated the temporal interactions between T cells and retinal endothelium in vitro. T cells and monolayers of cultured retinal EC's were cocuitured for periods of up to 4 hr. Ultrastructural analysis using both transmission and scanning electron microscopy revealed T cells adhering to the surface of the endothelium and lying underneath the monolayer. Using time-lapae videomicroscopy we have demonstrated that these lymphocytes migrate through the monolayer and not from the edges of the plaque. Over a 4 hr period T lymphocytes could be seen tracking over the surface oftbe monolayer migrating through and continuing to traffic underneath. Quantitation of this data showed that with both ocular and non-ocular antigen-specific T cell lines over 50,~ sf the cells migrate underneath the retinal EC monolayer by 4 hr. With peripheral lymph node (PLN) T cells, however, only 2-5% migrate underneath by 4 hr. By activating the PLN T cells with conconavalin A the number of cells underneath the EC monoiayer at 4 hr could he increased but did not approach those achieved with the ant;gen-specific T cell lines. Activation of the EC monolayer with interferon-¥ for 18- l hr did not alter the number of T cells migrating through the EC monolayer. The kinetics of migration of T cell subsets, selected by panning using antibodies against CD4 CD8, CD3 and CB45R (to distinguish between memory and naive CD4+ T cells) revealed no differences between these two groups.

NEURAL INVOLVEMENT IN SYSTEMIC IMMUNE-MEDIATED DISORDERS Burton Zweiman, MD. University of Pennsylvania School of Medicine, Philadelphia, PA. USA Nervous system (hiS) involvement occurs commonly in putative immune system disorders although pathogenetic mechanisms are still not well-defined. Manifestations are diverse, with difficulties at times in distinguishing them from NS effects of therapy and infectious complications. Understanding is also limited by the relative lack of pathognomonic laboratory findings. However, newer imaging and blood flow techniques may be helpful. In systemic lupus erythematosus, diffuse and focal involvement involvement of central and peripheral NS occurs commonly, often without evidence of local vasculitis but with selective association with anti-neuronal, anti-ribosomal P protein and anti-cardiolipin antibodies and immune complexes. In polyarterifis nodose, NS involvement frequently occurs early and is generally a poor prognostic sign. GiAntcell arteritis can invol~c cee,'a'al and peripheral NS as well as extra-cranial vessels. In Sjogren's syndrome, leukocytoclastic and mononuclear vasculopathy can involve central and peripheral NS. In contrast, NS involvement is relatively rare in scleroderma and occurs late in advanced rheumatoid arthritis. Parapmteinemia invoh,es the NS through vascular occlusion, inflammation and myeloid deposition. Proposed treatment programs will be discussed.