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P. B. Thomas, S. Selvam, D. Stevenson, J. D. Gray, A. K. Mircheff, J. E. Schechter, M. D. Trousdale; Autologous Mixed Cell Reaction and Induced Autoimmune Dacryoadenitis in a Rabbit Model: Evidence of CD4+ T Cell Involvement. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2315.
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Regulatory mechanisms involving CD4+ and CD8+ T cells are important in the maintenance of immune homeostasis. In Sjögren’s syndrome the infiltrates in lacrimal glands primarily consists of CD4+ T cells and IgG+ B cells. This study evaluates CD4+ cells in an ex vivo autologous acinar cell-peripheral blood lymphocyte (PBL) mixed cell reaction and in a rabbit model of induced experimental autoimmune dacryoadenitis
One inferior lacrimal gland was excised from each rabbit. Epithelial cells were purified and cultured for 2 days, gamma irradiated, and then co-cultured for 5 days with autologous PBL. Samples of the PBL and mixed cell reactions were assessed by FACS analysis after staining with CD4+ or CD8+ antibodies. The rest of the activated lymphocytes were injected into the remaining inferior lacrimal gland of the donor rabbit ("auto-adoptive transfer"). After 4 weeks, the inferior and superior lacrimal glands were removed for analysis. The glands were sectioned and immunostained to quantify the CD4+ and CD8+ immune cell populations.
The FACS analysis showed that the number of CD4+ T cells increased significantly in the mixed cell reactions compared to non-stimulated control lymphocytes. In contrast the number of CD8+ T cells did not change significantly in the mixed cell reactions. As reported previously, auto-adoptive transfer induced a vigorous dacryoadenitis with Sjögren’s-like periductal and perivenular foci. Immunohistochemistry revealed substantially more numerous CD4+ T cells in the lacrimal glands with induced dacryoadenitis compared to normal glands. The numbers of CD8+ T cells did not change significantly.
Rabbits with induced autoimmune dacryoadenitis showed clinical signs of dry eye and lacrimal gland histopathology. The majority of lymphocytes proliferating in the autologous mixed cell reactions and infiltrating the gland after autoadoptive transfer are CD4+ cells. These results suggest a strong involvement of CD4+ cells in the induction of autoimmune lacrimal gland disease.
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