Prenatal TCDD causes persistent modulation of the postnatal immune response, and exacerbates inflammatory disease, in 36-week-old lupus-like autoimmune SNF1 mice.

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.