Fluorescent transgenic reporter mice can be used for in vivo Imaging of lymphatic vessels and high endothelial venules in a Sjogren's model

Abstract Dramatic changes occur in the lymph node vasculature after immunization that affect antigen priming. There is a temporary defect in lymph flow and high endothelial venules (HEV) revert to an immature phenotype. To visualize these dynamic changes, we have made transgenic mice with red-fluorescent lymphatic vessels and green-fluorescent HEV that are suitable for live imaging. The lymphatic vessels of ProxTomxHec6st/eGFP reporter mice were successfully visualized in vivo using 2-photon laser scanning microscopy. We are interested in tertiary lymphoid organs (TLO) that develop in the autoimmune disease Sjögren’s-syndrome. Changes in lymphatic vessels and HEV may precede lymphocyte infiltration and autoantibody production. The presence of germinal centers in the minor salivary glands of Sjögren’s patients predicts the onset of extra-nodal lymphoma. We show lymphatic vessels, lymphocyte infiltration, HEV, T and B cell compartmentalization, and spontaneous lymphoma in BL/6 mice over 15 months old. We have made transgenic mice that express LTα and LTβ under the control of salivary amylase to model Sjögren’s syndrome. We are crossing the ProxTomxHec6st/eGFP reporter mice with mice that over-express lymphotoxin in their salivary glands, to understand the temporal sequence of the vascular changes that occur in Sjögren’s syndrome.