Changes in human peripheral blood mononuclear cell (HPBMC) populations and T-cell subsets associated with arsenic and polycyclic aromatic hydrocarbon exposures in a Bangladesh cohort

Abstract

Exposures to environmental arsenic (As) and polycyclic aromatic hydrocarbons (PAH) have been shown to independently cause dysregulation of immune function. Little data exists on the associations between combined exposures to As and PAH with immunotoxicity in humans. In this work we examined associations between As and PAH exposures with lymphoid cell populations in human peripheral blood mononuclear cells (PBMC), as well as alterations in differentiation and activation of B and T cells. Two hundred men, participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, were selected for the present study based on their exposure to As from drinking water and their cigarette smoking status. Blood and urine samples were collected from study participants. We utilized multiparameter flow cytometry in PBMC to identify immune cells (B, T, monocytes, NK) as well as the T-helper (Th) cell subsets (Th1, Th2, Th17, and Tregs) following ex vivo activation. We did not find evidence of interactions between As and PAH exposures. However, individual exposures (As or PAH) were associated with changes to immune cell populations, including Th cell subsets. Arsenic exposure was associated with an increase in the percentage of Th cells, and dose dependent changes in monocytes, NKT cells and a monocyte subset. Within the Th cell subset we found that Arsenic exposure was also associated with a significant increase in the percentage of circulating proinflammatory Th17 cells. PAH exposure was associated with changes in T cells, monocytes and T memory (Tmem) cells and with changes in Th, Th1, Th2 and Th17 subsets all of which were non-monotonic (dose dependent). Alterations of immune cell populations caused by environmental exposures to As and PAH may result in adverse health outcomes, such as changes in systemic inflammation, immune suppression, or autoimmunity.

Fig 1. Covariate-adjusted associations between UAs/Cr and cell surface markers.

Individual data points represent observations; solid lines represent estimated mean outcome vs. UAs/Cr adjusted for other variables in the model. The outcomes (A-B) were Th (CD4+) cells and monocytes (CD14+) and outcomes (C-D) were a subset of monocytes (CD14+CD16+) and NKT cells in logarithmic scales.

Fig 2. Covariate-adjusted associations between PAHs and cell surface markers.

Individual data points represent observations; solid lines represent estimated mean outcome vs. PAH-DNA adducts adjusted for other variables in the model. The outcomes (A-D) were T (CD3+), Th (CD4+), monocytes (CD14+), and Tmem (CD3+CD45+) cells in logarithmic scale.

Fig 3. Covariate-adjusted association between UAs/Cr and Th17 cells.

Individual data points represent observations; solid line represent estimated mean outcome Th17^1/3 vs. UAs/Cr adjusted for other variables in the model.

Fig 4. Covariate-adjusted association between PAH-DNA adducts and Th, Th1, Th2 and Th17 cells.

Individual data points represent observations; solid lines represent estimated mean outcome vs. PAH-DNA adducts adjusted for other variables in the model. The outcome variables (A-D) were Th, Th1^1/2, log(Th2), and Th17^1/3.