Adeno-associated virus-mediated IL-10 gene transfer suppresses lacrimal gland immunopathology in a rabbit model of autoimmune dacryoadenitis.
OBJECTIVE
To evaluate the effect of adeno-associated virus (AAV) vector-mediated viral (v)IL-10 gene expression on lacrimal gland (LG) immunopathology and ocular surface disease in a rabbit model of induced autoimmune dacryoadenitis (ID).


METHODS
Autologous peripheral blood lymphocytes, activated in a mixed-cell reaction when cocultured with purified rabbit lacrimal epithelial cells, induce a Sjögren's-like autoimmune dacryoadenitis when injected directly back into the donor animal's inferior LG. Four weeks after disease induction, AAV vector expressing the vIL-10 gene under control of a tetracycline-inducible promoter was injected into the inferior LG of the treatment group (ID/Rx), and doxycycline was fed orally to induce transgene expression. The ID group serving as control also received doxycycline. All LGs were removed 16 weeks after disease induction.


RESULTS
Clinical symptoms showed overall improvement in the ID/Rx group compared with the ID group. Histopathologic examination of the ID group's LG revealed scattered large lymphocytic foci and areas of altered or distorted acini, whereas the ID/Rx group had scattered small lymphocytic foci. The number of CD18(+) cells was almost fivefold lower in the ID/Rx group than in the ID group. Although the total number of RTLA(+) cells did not differ between the groups, the CD4/CD8 ratio was 16-fold smaller in the ID/Rx group.


CONCLUSIONS
Animals with experimentally induced autoimmune dacryoadenitis appeared to benefit from AAV-mediated vIL-10 gene transfer therapy. Quantitative immunohistochemical analysis suggested that the therapy might not have been simply immunosuppressive but rather supported the induction of CD8(+) regulatory cells.
Thomas
Padmaja B
PB
Ocular Surface Center, Doheny Eye Institute, Los Angeles, California 90033, USA.
Samant
Deedar M
DM
Selvam
Shivaram
S
Wei
Rui Hua
RH
Wang
Yanru
Y
Stevenson
Douglas
D
Schechter
Joel E
JE
Apparailly
Florence
F
Mircheff
Austin K
AK
Trousdale
Melvin D
MD
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018929:Cell Culture Techniques; D003607:Dacryocystitis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D007765:Lacrimal Apparatus / Q000276:immunology* / Q000473:pathology; D011817:Rabbits; D013666:Tears / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes
D016753:Interleukin-10