Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis.
Cell adhesion molecules are surface proteins important for cell migration and adhesion and are strongly expressed in eyes with inflammation. We studied the expression of two cell adhesion molecules: intercellular adhesion molecule-1 (ICAM-1, CD54) and lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) in mice with experimental autoimmune uveitis. B10.A mice were immunized with interphotoreceptor retinoid-binding protein and eyes were serially examined for expression of cell adhesion molecules using immunohistochemical staining. ICAM-1 was expressed on the vascular endothelium of the ciliary body and retina by 7 days after immunization, and LFA-1 was first expressed on some infiltrating inflammatory cells 9 days after immunization. Clear histologic evidence of ocular inflammation did not occur until 11 days after immunization. We then studied the effect of monoclonal antibodies against ICAM-1 and LFA-1 on the development of experimental autoimmune uveitis. Three groups of mice were immunized and treated for 21 days with daily intraperitoneal injections of rat monoclonal antibody against murine ICAM-1 or LFA-1 or with rat IgG as control. Ocular inflammation, graded clinically by examination of the fundus 14 and 21 days after immunization, was significantly decreased in animals treated with anti-ICAM-1 (P < 0.01 at Days 14 and 21) and with anti-LFA-1 antibody (P < 0.01 at Days 14 and 21). The intraocular inflammation graded histologically was also decreased in mice treated with anti-ICAM-1 and anti-LFA-1 antibody. This difference in the histologic grade of inflammation was statistically significant (P < 0.02) between mice treated with anti-ICAM-1 antibody and control mice and approached statistical significance (P < 0.10) in mice treated with anti-LFA-1 antibody compared to the control mice. Proliferative responses to lipopolysaccharide, PPD, and interphotoreceptor binding protein of lymphocytes obtained from the draining lymph nodes of mice treated with the antibodies were lower than those from the control mice, suggesting that cell-cell binding was impaired in treated mice. These data show that ICAM-1 is expressed in the eye before histologic evidence of inflammation, and that monoclonal antibodies against ICAM-1 and LFA-1 are effective in inhibiting experimental autoimmune uveitis in mice.
Whitcup
S M
SM
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892.
DeBarge
L R
LR
Caspi
R R
RR
Harning
R
R
Nussenblatt
R B
RB
Chan
C C
CC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000276:immunology*; D051379:Mice; D014605:Uveitis / Q000276:immunology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1