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D. M. Samant, P. B. Thomas, S. Selvam, D. Stevenson, J. D. Gray, J. E. Schechter, A. K. Mircheff, M. D. Trousdale; Autoimmune Dacryoadenitis Induced in Rabbits by Autoadoptive Transfer of CD4+- Enriched or CD4+- Depleted Lymphocytes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):426. doi: https://doi.org/.
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The characteristic lacrimal gland lesion in Sjögren’s syndrome is a lymphocytic focus consisting primarily of CD4+ T cells and IgG+ B cells. We previously found that isolated, primary cultured acinar cells express MHC Class II molecules and stimulate proliferation of autologous PBL in autologous mixed cell reactions (AMCR).The proliferating lymphocytes include pathogenic effector cells, since they induce focal lesions and ocular surface pathology when injected into the donor animals’ remaining lacrimal gland. Herein, we evaluated whether the proliferating, pathogenic cells are CD4+ T cells.
One inferior lacrimal gland was surgically excised from each rabbit. Acinar cells were purified, cultured for 2 days, gamma-irradiated, and then co-cultured for 5 days with purified autologous PBL. Lymphocytes from the AMCR were stained with rabbit-specific anti-CD4+ antibodies and separated by FACS. The CD4+ T cells were injected into the remaining inferior lacrimal gland of the donor rabbits. CD4+-depleted lymphocytes were injected into a second group of rabbits. After 4 weeks, ocular surface status was assessed, and the rabbits were sacrificed. Inferior and superior lacrimal glands were removed for histopathology.
FACS analysis revealed that CD4+ T cells preferentially proliferated in the mixed cell reactions, increasing from 20% to 80% of the cells counted. Rabbits injected with CD4+-enriched T cells developed clinical signs of severe, bilateral ocular surface disease; those injected with CD4+-depleted lymphocytes developed only moderate ocular surface disease. Rabbits injected with CD4+-enriched T cells also exhibited more severe lacrimal gland histopathology, with more eosinophils within acinar lumen, and more severely altered acinar morphology.
The majority of lymphocytes proliferating in mixed cell reactions with autologous acinar cells are CD4+ T cells. Autoadoptive transfer of these CD4+ T cells induces autoimmune dacryoadenitis with dramatic histopathology and severe dry eye. The results further suggest that lymphocytes which are weakly pathogenic and which do not express CD4 also proliferate in the autologous mixed cell reaction.
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