title: Prenatal TCDD causes persistent modulation of the postnatal immune response, and exacerbates inflammatory disease, in 36-week-old lupus-like autoimmune SNF1 mice.
abstract: BACKGROUND
  Prenatal exposure to the persistent environmental pollutant and model Ah receptor agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to permanently suppress postnatal cell-mediated immunity. More recently, skewing of select adult T and B cell responses toward enhanced inflammation has also been described in C57BL/6 mice after prenatal TCDD. This raises questions about adverse postnatal immune consequences of prenatal TCDD in animals genetically predisposed to inappropriate inflammatory responses.
  
  
  METHODS
  Lupus-prone SNF(1) mice were exposed to 0, 40, or 80 µg/kg TCDD on gestation day (gd) 12 and examined at 36 weeks-of-age for immunomodulatory effects that correlated with worsened lupus pathology.
  
  
  RESULTS
  Bone marrow pro- and large pre-B cells were decreased by prenatal TCDD, in both adult male and female mice, as were pre- and immature B cells. Splenic CD23(-) CD1(hi) and CD19(+) CD5(+) B cells were increased in males, as were B220(hi) B cells in females, further suggesting persistent disruption of B cell lymphopoiesis by prenatal TCDD. Female mice displayed decreased IL-10 production by ConA-activated splenocytes, while males underproduced IL-4. Autoreactive CD4(+) Vβ17a(+) spleen T cells were increased in both sexes by 80 µg/kg TCDD. Male mice but not females showed increased anti-ds DNA and cardiolipin autoantibody levels.
  
  
  CONCLUSIONS
  Prenatal TCDD augmented the hallmark indicators of SLE progression in the lupus-prone SNF(1) mice, including renal immune complex deposition, glomerulonephritis, and mesangial proliferation. Prenatal TCDD therefore caused persistent modulation of the postnatal immune response, and exacerbated inflammatory disease, in lupus-like autoimmune SNF(1) mice.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Amjad
authors.initials: A
authors.lastname: Mustafa
authors.forename: Steven
authors.initials: S
authors.lastname: Holladay
authors.forename: Sharon
authors.initials: S
authors.lastname: Witonsky
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmerman
authors.forename: Ashley
authors.initials: A
authors.lastname: Manari
authors.forename: Sheryl
authors.initials: S
authors.lastname: Countermarsh
authors.forename: Ebru
authors.initials: E
authors.lastname: Karpuzoglu
authors.forename: Robert
authors.initials: R
authors.lastname: Gogal
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002308:Cardiolipins / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003176:Complement C3 / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size / Q000187:drug effects; D010641:Phenotype; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D002308:Cardiolipins; D003176:Complement C3; D016207:Cytokines; D007074:Immunoglobulin G; D000072317:Polychlorinated Dibenzodioxins