Department of Anatomy and Radiology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382, United States.
Reprod Toxicol. 2011 Apr;31(3):312-8. doi: 10.1016/j.reprotox.2010.08.001. Epub 2010 Aug 20.
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.
两种免疫上不同的小鼠品系，C57BL/6 和 SNF(1)，被暴露于 TCDD 的中孕期剂量下。C57BL/6 小鼠具有高亲和力的芳香烃受体 (AhR)，对 TCDD 敏感。SNF(1)小鼠具有低亲和力的 AhR，但会自发发展出自免疫性肾炎。在 C57BL/6 小鼠后代中，24 周龄时出现了自身反应性 Vβ(+)CD4(+)17a 和 Vβ(+)CD3(+)T 细胞增加，雌性比雄性更为明显。雌性中 IFN-γ 升高，而雄性中 IL-10 升高。骨髓和脾脏中的 B 细胞系细胞出现表型改变，产前 TCDD 后循环自身抗体增加。雄性肾脏显示出明显的抗 IgG 和抗 C3 沉积，提示早期自身免疫性疾病。SNF(1)后代的雌性也表现出外周 Vβ(+)细胞增加，两性的自身抗体产生增加，雌性的 IFN-γ 产生增加。雄性 SNF(1)小鼠肾脏中的抗 IgG 和抗 C3 沉积增加。这两个小鼠模型在产前 TCDD 后均显示出明显的自身免疫增强特征。
