Suppression of experimental autoimmune uveitis in Lewis rats by oral administration of recombinant Escherichia coli expressing retinal S-antigen.
Experimental autoimmune uveitis (EAU) is an organ-specific T-lymphocyte-mediated autoimmune disease which serves as a model for several human ocular inflammations of an apparently autoimmune nature. S-antigen, a photoreceptor cell protein, is highly efficient in inducing EAU showing severe inflammation of the uveal tract and retina of the eye. We have demonstrated previously that recombinant Escherichia coli expressing retinal S-antigen induces EAU in Lewis rats. The oral administration of S-antigen prior to the uveitopathogenic challenge results in significant suppression of the disease and of the cellular responses. We examined the effect of oral administration of E. coli expressing retinal S-antigen on the development of EAU induced with native S-antigen in Lewis rats. Feeding rats with 1 mg of bacteria on Days 7, 5, 3, 2 and 1 prior to immunization with 50 micrograms of retinal S-antigen caused a significant suppression of the disease. Moderate suppression was found in animals fed 0.5 and 0.25 mg of recombinant bacteria. Oral feeding of 1 mg of JM105 transfected with plasmid alone had no significant effect on the subsequent induction of EAU by S-antigen. Feeding recombinant E. coli expressing retinal S-antigen before immunization significantly decreased the proliferative response of lymphocytes to native S-antigen in vitro. Our results indicate that recombinant microorganism-expressing autoantigen administered orally induces suppression of specific autoimmune disease as well as cellular response to particular autoantigen.
Singh
V K
VK
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Anand
R
R
Sharma
K
K
Agarwal
S S
SS
D000284:Administration, Oral; D000818:Animals; D019393:Arrestin / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000628:therapy
D019393:Arrestin; D011994:Recombinant Proteins