Lacrimal histopathology and ocular surface disease in a rabbit model of autoimmune dacryoadenitis.
OBJECTIVE
To study the effects of induced autoimmune dacryoadenitis on lacrimal gland function, histopathology, and ocular surface disease in a rabbit model.


METHODS
One lacrimal gland was surgically excised from each experimental rabbit, and epithelial cells were purified, cultured, irradiated, and then cocultured with autologous peripheral blood lymphocytes (PBLs) for 5 days. Autoimmune dacryoadenitis was induced by injecting the autologous mixed cell reactions (AMCRs) into the rabbit's remaining lacrimal gland. Normal rabbits and rabbits with both lacrimal glands injected with nonstimulated PBLs were examined as controls. Eyes were evaluated biweekly for 8 weeks by slit-lamp biomicroscopy, Schirmer testing, tear break-up time measurement, and rose bengal examination. Sections of lacrimal glands removed at 8 weeks post-operation were immunostained using antibodies against rabbit class II major histocompatibility complex molecule (MHC-II), CD4, CD8, CD18, and rabbit thymic lymphocyte antigen (RTLA). Relative numbers of positively stained cells were quantified with a ChromaVision image analysis system.


RESULTS
During an 8-week period, a continuous decrease in tear production and stability, accompanied by a continuous increase in rose bengal staining, occurred in eyes in which AMCR-PBL had been injected into the ipsilateral lacrimal glands. Similar, though generally less severe, changes occurred in eyes contralateral to the AMCR-PBL-injected eyes. No obvious changes by 8 weeks in these parameters were found in eyes in which the lacrimal glands had been injected with nonstimulated PBLs or in the lacrimal gland-excised eyes contralateral to normal eyes. Interstitial cells in normal lacrimal glands expressed CD18 and RTLA antigens, but few expressed CD4, CD8, or MHC-II. Focal mononuclear cell infiltrates were only found in lacrimal glands from animals with induced autoimmune dacryoadenitis. These cells were predominantly positive for CD4 (7.3-fold increase), RTLA (7.8-fold increase), or CD18 (42-fold increase). MHC-II expression in interstitial and ductal epithelial cells was also significantly greater in these animals than in control animals. The mononuclear cell infiltrates were frequently found enveloping venules, some of which appeared to be high endothelial cell venules. The ductal epithelium also contained CD4 and CD8 immunopositivity, within the epithelium, at the lumenal surface, or surrounding the ducts. Occasionally CD4 and CD8 immunopositive cells could be identified within the acinar lumens.


CONCLUSIONS
Injection of activated PBLs (i.e., AMCR-PBLs) in the lacrimal gland induces autoimmune dacryoadenitis with immunopathologic features similar to those of Sjögren's syndrome. The lacrimal immunopathology is accompanied by typical clinical manifestations of dry eye syndrome. The persistent significant dry eye does not appear to result just from failure of the diseased gland but from a more general dysfunction of the surface secretory tissues.
Zhu
Zejin
Z
Doheny Eye Institute, Los Angeles, CA 90033, USA.
Stevenson
Douglas
D
Schechter
Joel E
JE
Mircheff
Austin K
AK
Atkinson
Roscoe
R
Trousdale
Melvin D
MD
D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000150:complications* / Q000276:immunology / Q000473:pathology; D018821:CD18 Antigens / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003607:Dacryocystitis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology*; D011817:Rabbits; D013601:T-Lymphocytes / Q000166:cytology; D013666:Tears / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens