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Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on maternal immune response during pregnancy

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Abstract

Whether pregnancy-induced immunosuppression when combined with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could exacerbate immunotoxicity has not been previously investigated. The current study evaluated the immune status of C57BL/6 pregnant and virgin mice following exposure to TCDD. To this end, syngeneically pregnant or virgin female mice were injected intraperitoneally with 10 µg/kg TCDD. Pregnancy alone significantly decreased thymic cellularity and J11d expression as well as induced changes in T-cell subsets. TCDD treatment caused significant thymic atrophy in pregnant mice as early as 48 h after exposure, but this effect was apparent in virgin mice only after 72 h. TCDD treatment also caused more marked alterations in thymic T-cell subpopulations of pregnant mice when compared to the virgin mice, with a decrease in the percentage of double-positive T cells and an increase in the percentage of single-positive (sP CD4+ or sP CD8+) and double-negative T cells. Moreover, the proliferative responses of thymocytes, but not splenocytes, to mitogens were significantly altered in TCDD-treated pregnant mice when compared to the TCDD-treated virgin mice. Furthermore, no significant changes in the expression of CD4, CD8, B220 and NK1.1 markers were found in splenocytes from TCDD-treated virgin and pregnant mice. Immunization of mice with a superantigen caused a similar immunotoxic response in TCDD-treated pregnant and virgin mice with a decreased lymph node cellularity and lower percentages and cell numbers of Vβ3+ and Vβ11+ T cells. Together, the results of the current study demonstrate for the first time that pregnancy augments the sensitivity to TCDD-induced immunotoxicity in the thymus, but not in secondary lymphoid organs.

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Acknowledgements

This work was supported in part by the following grants from the US National Institutes of Health: R01ES09098, F31ES11562, R21DA014885, R01HL058641, R01AI053703 and R01DA016545. In addition, we like to state that this investigation complies with the current laws of the country in which the experiments were conducted.

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  1. Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA

    Iris A. Camacho & Mitzi Nagarkatti

  2. Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA

    Prakash S. Nagarkatti

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  1. Iris A. Camacho
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  2. Mitzi Nagarkatti
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Correspondence to Prakash S. Nagarkatti.

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Camacho, I.A., Nagarkatti, M. & Nagarkatti, P.S. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on maternal immune response during pregnancy. Arch Toxicol 78, 290–300 (2004). https://doi.org/10.1007/s00204-003-0538-8

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