Trials of vaccination against experimental autoimmune uveoretinitis with a T-cell receptor peptide.
T lymphocytes which mediate several experimental autoimmune diseases, including encephalomyelitis (EAE) and uveoretinitis (EAU) in Lewis rats, preferentially utilize V beta 8 gene product in their receptor. Vaccination against a V beta 8.2-derived peptide was reported to inhibit EAE induction and we report here on the effect of vaccination with this peptide on the development of EAU. Experimental rats were pretreated with the V beta 8.2 peptide, emulsified in adjuvant (CFA), whereas control animals were untreated or injected with saline in CFA. Rats of all groups were immunized 30 or 40 days later with the immunopathogenic antigen, emulsified in Mycobacterium-enriched CFA. Vaccination with CFA emulsions containing either the V beta 8.2 peptide or saline, remarkably inhibited the development of the tested diseases, as compared to the untreated controls. Vaccination with the V beta 8.2 peptide had variable effects in this study on disease development: it inhibited the S-antigen-induced EAU more than did treatment with CFA in four out of six experiments, had a similar effect to that of CFA in one experiment and enhanced the disease in another experiment. Conversely, vaccination with the V beta 8.2 peptide slightly enhanced the EAU induced by the interphotoreceptor retinoid-binding protein (IRBP), or its dominant determinant, in three of four experiments and had no apparent effect in the fourth experiment. In addition, we could not reproduce the reported protective effect of vaccination with the V beta 8.2 peptide against induction of EAE. Vaccination with the V beta 8.2 peptide also had no clear effect on the development of humoral or cellular immune responses against S-antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892.
Y
Y
Kawano
Y
Y
Sasamoto
S
S
Kotake
S R
SR
Thurau
B
B
Wiggert
I
I
Gery
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005136:Eye Proteins; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D010446:Peptide Fragments / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D012173:Retinitis / Q000276:immunology* / Q000517:prevention & control; D012177:Retinol-Binding Proteins; D014603:Uveal Diseases / Q000276:immunology* / Q000517:prevention & control; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C066890:T cell receptor-V(beta)8-39-59 peptide