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Perfluorooctanoic Acid Exposure Suppresses T-independent Antibody Responses
Citation:
Creech, N., Q. Hu, W. Williams, R. Luebke, AND J. Dewitt. Perfluorooctanoic Acid Exposure Suppresses T-independent Antibody Responses. Presented at Society of Toxicology Annual Meeting, March 10 - 14, 2013.
Impact/Purpose:
These studies were done to investigate potential immune system cellular targets of PFOA, to gain a better understanding of how the chemical reduces the response to immunization. This compound is widely distributed in the environment, is persistent, and is routinely identified in human blood samples. The results may be useful in determining the relative sensitivity of the rodent and human immune systems, thus improving our understanding of potential human risk.
Description:
Exposure to 3.75mg/kg of perfluoroocatnoic acid (PFOA) for 15d suppresses T-dependent antibody responses (TDAR), suggesting that T helper cells and/or B cells/plasma cells may be impacted. This study evaluated effects of PFOA exposure on the T cell-independent antibody response (TIAR) to dinitrophenyl-ficoll (DNP). Adult female C57BL/6 mice were given 0, 0.94, 1.88, 3.75, or 7.5 mg/kg of PFOA in drinking water for 15d and immunized with 1 g of DNP in 0.2 ml of sterile saline on d11 of dosing. Seven days after immunizations and 3d after dosing ended, animals were euthanized and bled; sera were evaluated for IgM anti-DNP titers by ELISA. PFOA exposure did not alter body or lymphoid organ weights. Mean IgM serum titers of animals dosed with ≥ 1.88 mg/kg PFOA were statistically suppressed, regardless of dose, by approximately 10% relative to control responses. Splenic B and T cell subset phenotypes were evaluated in separate groups of animals dosed with 0, 3.75 or 7.5 mg/kg of PFOA for 10, 13, or 15d. Animals exposed for 13 or 15d were immunized with sheep erythrocytes on d11 of dosing. In animals exposed for 15d, the mean percentage of B cells was increased by all doses. Within the CD3+ T cell population, the following changes were observed in the mean percentage of cells: CD4+CD8- T cells were increased at doses of 3.75 and 7.5 mg/kg after 10, 13, and 15d of exposure; CD4+CD8+ T cells were increased after 13d of exposure across all doses relative to 10 and 15d of exposure; CD4-CD8+ and CD4-CD8- T cells had dose and duration interactions, with no clear effect of dose or duration of exposure. Overall, PFOA exposure did not reduce splenic B or T cell populations. Suppression of TDAR and TIAR, in the absence of obvious lymphocyte subpopulation disruption suggests that effects on humoral immunity are likely mediated, at least in part, by altered B cell/plasma cell function. This abstract does not represent EPA policy.