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International Immunology, Vol. 11, No. 8, 1307-1312, August 1999
© 1999 Japanese Society for Immunology

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

Bing Sun, Shu-Hui Sun, Chi-Chao Chan, Barbara Wiggert1 and Rachel R. Caspi

Laboratory of Immunology, and
1 Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD 20892, USA

Correspondence to: R. R. Caspi, Laboratory of Immunology, NEI/NIH, 10 Center Drive, MSC 1857, 10/10N222, Bethesda, MD 20892-1857, USA

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.

Keywords: autoimmunity, cytokines, rodent, Th1/Th2, uveitis

Transmitting editor: J. A. Berzofsky


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