Autoimmunity to a pathogenic retinal antigen begins as a balanced cytokine response that polarizes towards type 1 in a disease-susceptible and towards type 2 in a disease-resistant genotype.
Susceptible, but not resistant, strains of rodents immunized for induction of experimental autoimmune uveitis (EAU) with the uveitogenic protein interphotoreceptor retinoid-binding protein (IRBP) exhibit a type 1 response at the time of disease expression. Here we investigate the evolution of this response using the prototypic EAU-susceptible and EAU-resistant mouse strains, B10.A and BALB/c. Disease severity and IRBP-specific responses (proliferation, cytokines and antibody isotypes) were evaluated 7, 14 and 21 days after uveitogenic immunization. B10.A mice initially exhibited an IgG1-dominated antibody response, and their lymph node cells produced IL-4 and IL-5 in addition to IFN-gamma. On day 14 and 21, however, the IgG2a isotype became predominant, and the primed lymph node cells produced mainly IFN-gamma and IL-12. B10.A mice developed EAU before day 14. BALB/c mice initially produced IL-12 and IFN-gamma in addition to IL-5, IL-4 and IL-10. At later time points IL-12 and IFN-gamma production diminished, and IL-4, IL-5 and IL-10 increased. An IgG1-dominated antibody response was maintained throughout. BALB/c mice failed to develop EAU even at day 21. Thus, both susceptible and resistant genotypes initially mount a balanced, type 0-like cytokine response to a uveitogenic challenge, that subsequently polarizes towards type 1 in the susceptible strain and towards type 2 in the resistant strain.
Sun
B
B
Laboratory of Immunology, and Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD 20892, USA.
Sun
S H
SH
Chan
C C
CC
Wiggert
B
B
Caspi
R R
RR
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D005136:Eye Proteins; D005260:Female; D007114:Immunization; D007132:Immunoglobulin Isotypes; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012177:Retinol-Binding Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D000099214:Retinol-Binding Proteins, Interstitial
D001323:Autoantibodies; D016207:Cytokines; D005136:Eye Proteins; D007132:Immunoglobulin Isotypes; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial