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P. B. Thomas, D. M. Samant, S. Selvam, D. Stevenson, J. E. Schechter, A. K. Mircheff, M. D. Trousdale; Autoimmune Dacryoadenitis Induced in Rabbits by Intravenous Injection of Autologous Lymphocytes Activated Ex Vivo Against Lacrimal Antigens. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3394.
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Autologous peripheral blood lymphocytes (PBL), activated in a mixed cell reaction when co-cultured with purified rabbit lacrimal epithelial cells, induce a Sjögren’s-like autoimmune dacryoadenitis when injected directly back into the donor animal’s remaining inferior lacrimal gland (LG) or subcutaneously at a remote site. The purpose of the present study was to determine the ability of intravenously injected (IV) autologous stimulated lymphocytes to home to the LG and induce dacryoadenitis.
One inferior LG was surgically excised from each rabbit. Acinar epithelial cells were purified, cultured for 2 days, gamma-irradiated, and then co-cultured for 5 days with purified autologous PBL. Activated lymphocytes were used for autoadoptive transfer.
Tear production was reduced 50% by 4 weeks and tear break up time was 70% less than normal. Ocular surface defects assessed by rose bengal staining were not as pronounced as after direct injection. However, 4 weeks after IV injection, unique areas of streaming lymphocytes were observed and lymphocytes were found close to interlobular and intralobar ducts. At 8 weeks LG showed clusters of abnormal lacrimal acinar cells and streaming lymphocytes. Immunohistochemical staining revealed that inflammatory infiltrates were composed of predominantly CD4+ T cells.
Regardless of the injection site lymphocytes activated against lacrimal antigens can home to the lacrimal gland and are capable of inducing autoimmune dacryoadenitis, suggesting that the LG constitutively contains not only antigen presenting cells displaying potentially pathogenic autoantigen epitopes, but also chemokines and homing molecules that recruit CD4+ T cells; we propose that these mediators normally recruit regulatory cells, but also recruit pathogenic effector cells that have been activated in peripheral lymphoid tissues.
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