Abstract
Two immunologically different mouse strains, C57BL/6 and SNF(1), were exposed to a mid-gestation dose of TCDD. The C57BL/6 mouse has a high-affinity aryl hydrocarbon receptor (AhR) and is sensitive to TCDD. The SNF(1) mouse has a low-affinity AhR but spontaneously develops autoimmune nephritis. Autoreactive Vβ(+)CD4(+)17a and Vβ(+)CD3(+) T cells were increased at 24-weeks-of-age in offspring of C57BL/6 mice, more so in females than males. The cytokine IFN-γ was elevated in the females, while IL-10 was elevated in males. Phenotypic changes in B-lineage cells were present in bone marrow and spleen, and circulating autoantibodies were increased after prenatal TCDD. Kidneys of males showed significant anti-IgG and anti-C3 deposition, suggesting early-stage autoimmune disease. The SNF(1) offspring similarly showed increased peripheral Vβ(+) cells in the females, increased autoantibody production in both sexes, and increased IFN-γ production in females. Male SNF(1) mice had increased anti-IgG and anti-C3 deposition in kidneys. Both mouse models therefore showed clear signatures of enhanced autoimmunity after prenatal TCDD.