Genetic susceptibility to experimental autoimmune uveoretinitis in the rat is associated with an elevated Th1 response.
This study examines whether genetic susceptibility vs genetic resistance to experimental autoimmune uveoretinitis (EAU) are connected to a predisposition to mount a Th1-dominated (IFN-gamma high, IL-4 low) vs a Th2-dominated (IL-4 high, lFN-gamma low) response. Lewis rats developed disease with high incidence after immunization with the uveitogenic peptide R16, whereas F344 rats were resistant. Primed lymph node cells from both strains proliferated in culture in response to R16. However, while the Lewis cultures transferred EAU to syngeneic recipients, those of F344 did not. The Lewis cultures produced substantially more IFN-gamma mRNA and protein in response to R16, than did those of F344. Both strains made low levels of IL-10 mRNA and IL-4 mRNA. Unlike the primary cultures, long-term (R16-specific) T cell lines derived from each of the strains transferred EAU equally well to their respective recipients, and produced similar, high levels of IFN-gamma mRNA and protein. Treatment of F344 with Bordetella pertussis toxin concurrently with immunization abrogated its resistance, enhanced Ag-specific IFN-gamma production in culture, and yielded a primed cell population capable of transferring EAU. Conversely, immunization of Lewis rats with R16 in IFA induced little or no disease; the primed cells produced minimal amounts of IFN-gamma and did not transfer EAU. However, addition of IL-12 into the culture resulted in a highly pathogenic, IFN-gamma-producing cell population. We conclude that genetic susceptibility to ocular autoimmunity in this model is connected to an elevated Th1 response. Genetic resistance, however, does not seem to involve an elevated Th2 response, but rather an inhibited development of Th1-like effector cells.
Caspi
R R
RR
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Silver
P B
PB
Chan
C C
CC
Sun
B
B
Agarwal
R K
RK
Wells
J
J
Oddo
S
S
Fujino
Y
Y
Najafian
F
F
Wilder
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D008213:Lymphocyte Activation / Q000235:genetics*; D008969:Molecular Sequence Data; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology*; D014605:Uveitis / Q000209:etiology / Q000235:genetics* / Q000276:immunology*