Purpose: Autologous peripheral blood lymphocytes, activated in a mixed cell reaction when cocultured with purified rabbit lacrimal epithelial cells, are known to induce a severe autoimmune dacryoadenitis when injected directly into the donor animal's remaining inferior lacrimal gland (LG) or subcutaneously at a site remote from the LG. The purpose of the present study was to determine the ability of intravenously (IV) injected autologous stimulated lymphocytes to home to the LG and salivary gland (SG) and induce disease.
Methods: One inferior LG was surgically excised from each rabbit. Acinar epithelial cells were purified, cultured for 2 days, gamma-irradiated, and cocultured for 5 days with purified autologous peripheral blood lymphocytes. The activated lymphocytes were used for autoadoptive transfer.
Results: Tear production was reduced 50% by 4 weeks and tear breakup time was 70% less than normal. Ocular surface defects assessed by rose bengal staining were present but not as pronounced as after direct injection. Four weeks after IV injection, as after direct injection, glands contained large infiltrates composed of predominantly CD4+ T cells close to interlobular and intralobular ducts; however, they also contained unique areas of streaming lymphocytes. Histopathology at 8 weeks was more severe than at 4 weeks, and SG also showed clusters of abnormal epithelial cells and streaming lymphocytes.
Conclusions: Lymphocytes activated against lacrimal antigens and injected IV can home to the LG and SG and initiate autoimmune processes, suggesting that these sites constitutively contain not only antigen-presenting cells displaying potentially pathogenic autoantigen epitopes but also chemokines and homing molecules that recruit CD4+ T cells. This new rabbit model more closely mimics Sjögren syndrome, in that SG manifestations accompany the LG disease. It should be well suited to elucidating Sjögren pathogenesis and pathophysiology and to evaluating experimental therapies.
*Ocular Surface Center, Doheny Eye Institute, Los Angeles, CA
†Tianjin Medical University Eye Center, Tianjin, China
‡Department of Ophthalmology
§Department of Cell and Neurobiology
¶Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Reprints: Melvin D. Trousdale, Doheny Eye Institute, 1450 San Pablo St, DVRC204A, Los Angeles, CA 90033 (e-mail: firstname.lastname@example.org).
Supported by grants EY12689, EY05801, EY10550, and EY03040 (Doheny Eye Institute Core grants); an unrestricted grant from Research to Prevent Blindness, Inc.; and a grant from Allergan (M.D.T.).
The authors state that they have no conflicts of interest to disclose.
Received March 28, 2011
Accepted July 8, 2011