Experimental Autoimmune Dacryoadenitis Induced by Autologous Transfer of Activated Lymphocytes in Rabbits

Abstract

Abstract: : Purpose: To establish a rabbit model of experimental dacryoadenitis by subcutaneous injection of the lymphocytes activated in autologous mixed cell reactions. Methods: Peripheral blood lymphocytes were stimulated by 5 day co–culture with autologous acinar cells isolated from one lacrimal gland. Activated lymphocytes were injected subcutaneously back into the donor. Rabbits injected with non–activated cultured peripheral autologous lymphocytes served as controls. Clinical evaluation, including Schirmer’s test, tear break–up time, and rose bengal staining, were performed 2 and 4 weeks post injection. Superior and inferior lacrimal glands and conjunctiva were processed for H&E staining and immunohistochemical staining 4 weeks post injection. Results: By 4 weeks post injection, a significant reduction of tear break–up time and increased rose bengal scores were observed in the rabbits that received subcutaneous injections of activated lymphocytes; however, the decline of tear production was borderline in this group. The lacrimal glands had an abundance of lymphocytes in the interacinar areas, often concentrated around venules. Degenerating acini were seen in some fields. The accumulations of lymphocytes were observed in both the superior and inferior lacrimal glands, as well as in the conjunctiva of the animals with induced disease. In contrast, tissues from the control animals had fewer lymphocyte infiltrates, and acini appeared normal. Conclusions: Adoptive transfer of autologous activated lymphocytes induces a disease with the clinical features of dry eye and pathologic features of autoimmune dacryoadenitis. This result suggests that autoantigen presenting cells are present in normal lacrimal glands and become pathogenic in the presence of activated, autoreactive lymphocytes.

Keywords: cornea: tears/tear film/dry eye • autoimmune disease