Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) modify in vitro mitogen- and antigen-induced human peripheral blood mononuclear cell (PBMC) responses

ABSTRACT

Environmental contaminants perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are present in human serum at the highest concentration among all per- and polyfluoroalkyl substances (PFAS). Serum concentrations as high as 500 ng and 3000 ng PFOA/ml have been detected in individuals living near contamination sites and those occupationally exposed, respectively. Animal and human studies indicated that PFOA and PFOS at these serum concentrations perturb the immune system. The aim of this study was to examine the effects of in vitro exposure of human peripheral blood mononuclear cells (PBMC) to 1, 10, or 100 µM PFOA or PFOS in a medium with serum (RPMI-1640 + 5% human AB serum) on the measurement of proliferation, T cell activation, generation of memory T cells, and cytokine production/secretion. In addition, these immune system parameters were assessed for PBMC in a serum-free medium (OpSFM), which was stimulated with phytohemagglutinin (PHA) (2.5 µg/ml) or influenza vaccine antigen (0.625 µg/ml Flu Ag). PFOS decreased proliferation stimulated by PHA or Flu Ag. With Flu Ag stimulation, PFOA and PFOS inhibited the generation of memory T cells in a concentration-dependent manner. In OpSFM, PFOA and PFOS produced no marked change in proliferation and no inhibition of T cell activation. Cytokines measured in the media with Luminex methodology indicated decreased PBMC secretion of IFN-γ by PFOA and PFOS in medium with serum, but no alteration in OpSFM. The results indicated that changes in immune parameters due to PFOA or PFOS following Flu Ag stimulation are medium (±serum) dependent.

KEYWORDS:

• Perfluoroalkyl substances
• human PBMC cell culture
• antigenic/mitogenic stimulation
• naïve/memory cells
• serum free cultures
• T cells
• B cells

Acknowlegments

We thank the Tissue Culture Facility of Wadsworth Center for supplying the RPMI1640 medium. We thank Richard Cole, director of the Advanced Light Microscopy & Image Analysis Core, for taking pictures of our cells in culture. We thank Kevin Manley for his technical assistance with the cytokine concentration measurements. We also thank Heidi Dillenbeck for her phlebotomy services and our New York State Department of Health (NYSDOH) blood donors, who volunteered to donate blood for NYSDOH IRB Protocol 98-108.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

The data that support the findings of this study are available from the corresponding author, J. K-J., upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.