Suppression of established experimental autoimmune uveitis by anti-LFA-1alpha Ab.
OBJECTIVE
To identify costimulatory molecules that are important in the effector phase of experimental autoimmune uveitis (EAU).


METHODS
EAU was induced in C57BL/6 (B6) mice by transfer of activated T cells specific for the interphotoreceptor-binding protein (IRBP) 1-20 peptide. The animals were then treated with and without anti-leukocyte function associated antigen (LFA)-1alpha mAb, at day 0 or 10 (disease onset) after T-cell transfer. Clinical signs of inflammation, ocular histology, and infiltrated inflammatory cells in the eye were compared. The primary and secondary proliferative responses of uveitogenic CD4 and CD8 T cells were tested after treatment with costimulatory blockers in vivo and in vitro. Moreover, the abilities of uveitogenic T cell trafficking and their interaction with retinal astrocytes were examined.


RESULTS
Anti-LFA-1alpha Abs caused significant suppression of disease when administered either at the time of effector uveitogenic T cell transfer or at disease onset. Studies of the mechanisms by which anti-LFA-1alpha Ab inhibits the effector phase of uveitis demonstrated that it blocks multiple pathogenic events of uveitis mediated by IRBP-specific uveitogenic T cells, including the activation of T cells outside and inside the eye and the trafficking of activated autoreactive T cells into the inflammatory site. In addition, Ab treatment selectively suppressed the activation and expansion of pathogenic, but not regulatory, T cells in vivo.


CONCLUSIONS
Anti-LFA-1alpha Abs are potent inhibitors of established autoimmune uveitis and that such treatment may be applicable not only for the prevention, but also the treatment, of T-cell-mediated autoimmune diseases.
Ke
Yan
Y
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky 40202, USA.
Sun
Deming
D
Zhang
Ping
P
Jiang
Guomin
G
Kaplan
Henry J
HJ
Shao
Hui
H
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001253:Astrocytes / Q000166:cytology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012177:Retinol-Binding Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D000911:Antibodies, Monoclonal; D005136:Eye Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial