A promising therapeutic approach for treatment of posterior uveitis: recombinant T cell receptor ligand protects Lewis rats from acute and recurrent experimental autoimmune uveitis.
BACKGROUND
Chronic autoimmune uveitis is a major cause of vision loss from intraocular inflammation in humans. In this study we report that a recombinant TCR ligand (RTL220) composed of the alpha1 and beta1 domains of MHC class II molecules linked to the uveitogenic interphotoreceptor retinoid-binding protein (IRBP) 1177-1191 peptide is effective in the suppression of acute and recurrent experimental autoimmune uveitis (EAU).


METHODS
EAU was induced with IRBP1177-1191 peptide or by adoptive transfer of specific T cells in Lewis rats. The rats received 5 doses of RTL220 subcutaneously every other day starting at the onset of clinic signs of EAU.


RESULTS
The administration of RTL220 resulted in a delayed onset and a significant amelioration of the disease severity at clinical levels and showed protection of the retina from inflammatory damage at histological levels. In treatment of recurrent EAU, RTL220 administrated at the first or second onset of clinical disease significantly inhibited EAU, modulated immune responses and provided protection from relapses of uveitis. The systemic and local proinflammatory cytokines were significantly reduced, including IL-17. There was local and systemic increase in IL-10 and reduction in the expression of the proinflammatory chemokines CCL2, CCL3 and CCL5.


CONCLUSIONS
Our studies demonstrate a successful treatment of acute and recurrent EAU with RTL220, which effectively suppressed the recurrence of inflammation and reversed clinical and histological EAU by altering cytokine and chemokine expression. These findings strongly support a possible clinical application of this novel class of peptide/MHC class II drugs for patients with autoimmune uveitis.
Ocular Immunology Laboratory, Department of Ophthalmology, Oregon Health and Science University, Portland, OR 97239, USA. adamusg @ ohsu.edu
Grazyna
G
Adamus
Landon J
LJ
Karren
Jeff
J
Mooney
Gregory G
GG
Burrows
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007279:Injections, Subcutaneous; D008024:Ligands; D010446:Peptide Fragments; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D012008:Recurrence; D012177:Retinol-Binding Proteins; D013601:T-Lymphocytes; D015866:Uveitis, Posterior / Q000473:pathology / Q000517:prevention & control*
D016207:Cytokines; D008024:Ligands; D010446:Peptide Fragments; C552936:RTL220 protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D012177:Retinol-Binding Proteins; C084432:immunodominant R16 protein, rat