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Safinaz Mostafa, Vanessa Seamon, Ana Maria Azzarolo; Lymphocytic Infiltration Precedes the Lacrimal Gland Cell Death in the Pathogenesis of Sjögren’s Syndrome (SS). Invest. Ophthalmol. Vis. Sci. 2011;52(14):3718.
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A characteristic hallmark of SS is lymphocytic infiltration into the lacrimal glands. The lymphocytic infiltrates consist mainly of CD4+, CD8+ T cells and B220+ B cells. However, the cause and time course of this infiltration in SS remains to be elucidated. We have been studying the disease progression using ovariectomized (OVX) NOD.B10.H2b mice, which provides a model of menopause combined with a predisposed genetic background to SS. Recently, we have shown an increase in lacrimal gland cells apoptosis at 7 and 21post-OVX. In this study we investigated the time course of lymphocytic infiltration that occurs in the lacrimal gland after ovariectomy.
Six week old C57BL/10SnJ, control and NOD.B10-H2b, mouse model of SS, were ovariectomized or sham operated. After 3, 7 and 21 days, the lacrimal glands were removed and processed for immunocytochemistry. The numbers of T and B lymphocytes were measured by using the Avidin-Biotin Complex method. CD4+ and CD8+ stained cells were used as a marker of T cells, and B220+ stained cells were used as a marker of B cells. Quantification of the stained positive cells was done using an Image Pro Plus analysis system.
Ovariectomized NOD mice showed significant increases in the numbers of CD4+, CD8+ T cells and B220+ B cells at 3, 7 and 21 post-OVX days compared to the sham operated groups. Slight, but significant increases were seen in the number of CD4+ T cells and B220+ B cells only at 3 and 7 post-OVX days in the C57BL/10SnJ mice compared to the sham operated groups.
Our results suggest that decreased circulating levels of sex hormones trigger an immune response in earlier stages of the disease progression. This immune response precedes the increase in apoptotic events in the lacrimal glands of ovariectomized mice. The lymphocytic infiltration was more severe and persistent in the predisposed genetic background.
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