Prenatal TCDD in mice increases adult autoimmunity.
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.
Holladay
Steven D
SD
Department of Anatomy and Radiology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382, United States. sdholl@uga.edu
Mustafa
Amjad
A
Gogal
Robert M
RM
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012737:Sex Factors; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
D004785:Environmental Pollutants; D000949:Histocompatibility Antigens Class II; D000072317:Polychlorinated Dibenzodioxins; D016753:Interleukin-10; D007371:Interferon-gamma