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.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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.

Int Immunol. 1999 Aug;11(8):1307-12. Unique Identifier : AIDSLINE MED/99352261
Sun B; Sun SH; Chan CC; Wiggert B; Caspi RR; Laboratory of Immunology, and Laboratory of Retinal Cell and; Molecular Biology, National Eye Institute, NIH, Bethesda, MD; 20892, USA.

Abstract: 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: JOURNAL ARTICLE Animal Autoantibodies/BLOOD Autoimmune Diseases/*IMMUNOLOGY Autoimmunity Cytokines/BIOSYNTHESIS Disease Susceptibility Female Immunization Immunoglobulin Isotypes Lymph Nodes/IMMUNOLOGY Lymphocyte Transformation Mice Mice, Inbred BALB C Retinol-Binding Proteins/*IMMUNOLOGY Th1 Cells/*IMMUNOLOGY Th2 Cells/*IMMUNOLOGY Uveitis/CHEMICALLY INDUCED/*IMMUNOLOGY/PHYSIOPATHOLOGY
991230
A99C1074

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