Autoimmunity to a pathogenic retinal antigen begins as a balanced cytokineresponse that polarizes towards type 1 in a disease-susceptible and towards type 2 in a disease-resistant genotype
B. Sun et al., Autoimmunity to a pathogenic retinal antigen begins as a balanced cytokineresponse that polarizes towards type 1 in a disease-susceptible and towards type 2 in a disease-resistant genotype, INT IMMUNOL, 11(8), 1999, pp. 1307-1312
Susceptible, but not resistant, strains of rodents immunized for induction
of experimental autoimmune uveitis (EAU) with the uveitogenic protein inter
photoreceptor retinoid-binding protein (IRBP) exhibit a type 1 response at
the time of disease expression. Here we investigate the evolution of this r
esponse using the prototypic EAU-susceptible and EAU-resistant mouse strain
s, B10.A and BALB/c, Disease severity and IRBP-specific responses (prolifer
ation, cytokines and antibody isotypes) were evaluated 7, 14 and 21 days af
ter uveitogenic immunization. B10.A mice initially exhibited an IgG1-domina
ted 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 produ
ced 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. B
ALB/c mice failed to develop EAU even at day 21, Thus, both susceptible and
resistant genotypes initially mount a balanced, type 0-like cytokine respo
nse to a uveitogenic challenge, that subsequently polarizes towards type 1
in the susceptible strain and towards type 2 in the resistant strain.