Lacrimal Gland Involvement in Graft-Versus-Host Disease: A Murine Model

Abstract

To describe lacrimal gland involvement in a murine model of acute graft-versus-host disease (GVHD). Histopathologic examination was performed on lacrimal glands of mice affected by GVHD at 1, 2, 4, and 6 weeks after allogeneic bone marrow transplantation (BMT). Histopathologic scoring, based on characteristic GVHD findings in human disease involved evaluation of periductal inflammation, apoptosis, ductal stasis, ductal debris, and fibrosis. CD3, CD4, CD8, CD20, and CD68 antibodies were used to stain leukocyte subsets in GVHD lacrimal gland infiltrates. Lacrimal glands from syngeneic BMT mice were used in control experiments. Patchy periductal inflammation and focal fibrosis were significantly elevated as early as 2 weeks after allogeneic BMT. Histopathologic scoring of lacrimal glands after allogeneic BMT was significantly different at 4 (P = 0.005) and 6 (P < 0.0001) weeks when compared with scores in syngeneic control mice. The leukocytes in lacrimal gland GVHD infiltrates were predominately CD3+ T lymphocytes, most of which were CD8+, with fewer CD4+ cells present. This study describes the first murine model of lacrimal gland GVHD with features that closely mimic those described in human disease and indicates that lacrimal involvement occurs in acute GVHD.