CD4+ helper T cells are an important cell of the immune system. One key factor in the mediation of the immune system in general, and T cells in particular, is the female sex hormone estrogen. Abnormal estrogen levels are associated with a variety of conditions, including autoimmune diseases, and several types of cancer, including breast cancer. BPA is a well-known estrogen mimicking compound, used in the manufacturing of plastics, epoxy resins, and polystyrenes. As the negative effects of BPA become more apparent, many BPA substitutes have been developed. While the effect of estrogen on T cells is understood, the effect of estrogen mimics like BPA is less certain. The aim of this research was to determine if BPA substitutes affect the differentiation and function of CD4+ T cells, and if they have estrogenic activity in these cells. Murine CD4+ T cells were stimulated to encourage differentiation into T cell subsets Th1, Th2, Th17, and Treg. T cells were cultured with BPA substitutes BPAF, BPS, TMBPF, BHPF, and DD-70, as well as BPA, estrogen, media, and DMSO. BPA, BPAF, and BPS were all found to mimic estrogen by skewing the Th1/Th2 immune profile toward a Th2 profile by suppressing cytokine secretion and master transcription factor expression in proinflammatory Th1 and Th17 cells and increasing cytokine secretion and master transcription factor expression in anti-inflammatory Th2 and Treg cells. TMBPF, BHPF, and DD-70 were found to not mimic estrogen. Additionally, BPA, BPAF, and BPS were found to increase ERα activation, like estrogen itself, while TMBPF, BHPF, and DD-70 did not. Overall, each of the BPA substitutes has the potential to negatively effect human health, and further research is needed to determine the safest alternatives to BPA.
Poole, Cassandra, "The Effect of Bisphenol A (BPA) Substitutes on CD4+ T Cell Immunity" (2023). Longwood Senior Theses. 29.