The kinetics of cell surface receptor expression in children perinatally exposed to polychlorinated biphenyls

Abstract

Exposure to polychlorinated biphenyls (PCBs) during pre-natal and early life can alter normal immune system development. Blood specimens from newborns, 6-, and 16-month-old infants were collected in the Michalovce and Svidnik/Stropkov districts, areas with, respectively, high and low environmental PCB contamination, and lymphocyte receptor expression was evaluated by multi-color flow cytometry. The results indicate that the percentage of lymphoid dendritic cells (DC) and naïve/resting T-lymphocytes were significantly increased at 6-months in Michalovce as compared to the same cell types in cord blood samples (p < 0.001), whereas natural regulatory T-lymphocytes and suppressor inducer T-lymphocytes were reduced (p < 0.001). Overall, a positive linear correlation of terminally differentiated effector memory (TEM) T-lymphocyte population with age, but a negative linear correlation for myeloid DC from birth to 6-months in both regions were found. Michalovce samples indicated significantly higher expression of memory T-lymphocytes (birth, 6^th, and 16^th month), TEM T-lymphocytes (birth and 6^th month), and lymphoid DC (6^th month) compared to the Svidnik/Stropkov regions. After adjustment for relevant covariates, such as maternal age, parity, season of birth, breastfeeding, birth weight, and gender, the myeloid DC, suppressor inducer T-lymphocytes, truly naïve helper/inducer T-lymphocytes, and TEM T-lymphocytes remained significantly different between districts in cord blood samples. The multivariate analysis models for 6- and 16-month samples showed district differences in all cellular determinants, except for lymphoid DC and macrophage-like cells. This study provides the first evidence that pre-natal and early post-natal exposure to PCBs affects the dynamics of cell surface receptor expression on lymphoid DC and DC-like cells, suggesting impaired immunologic development following pre-natal and early post-natal PCB exposure.

Keywords::

• Cell surface marker
• polychlorinated biphenyls
• environmental pollution
• cord blood
• infant
• pre-natal exposure
• post-natal exposure
• dendritic cells
• macrophage-like cells
• naïve T-cells
• memory T-cells

Acknowledgments

This work was supported by the US NIH grant no. R01-CA096525, by the grant of the Slovak Ministry of Health, no. 2005/31-SZU-09, and the 6^th FP EU research projects ‘HEIMTSA’ (no. GOCE-CT-2006-036913-2) and ‘INTARESE’ (no. GOCE 018385). The authors wish to thank Dr Allen Silverstone for his excellent advice on immunophenotyping in the early parts of the project. In addition, we thank Mikulas Krnac and Zuzana Kormancikova for their technical assistance and we wish to thank our regional cooperators and all mothers with children who participated in the study.

Declaration of interest

The authors report no conflicts of interest. The authors alone are alone responsible for the content and writing of the paper.

Appendix

Tables A1–A3 present results of the major associations between variables (e.g., maternal smoking, age, parity, season of birth, etc.) and cell surface receptor changes in children. The descriptive characteristics of DC, macrophage- and DC-like cells and CD4⁺ T-lymphocyte subtypes in all infants of the cohort are shown in Tables A4 and A5. The impact of age on the dynamics of cell surface receptors expression over the period from birth through infancy was determined in the total study group (Michalovce and Svidnik/Stropkov), regardless of PCB contamination (Table A6).

Table A1.  The major differences between variables (i.e., parity, maternal smoking, season of birth) and cell surface receptor changes in children.

Table A2.  The major differences between variables (i.e., ethnicity, gender, breastfeeding) and cell surface receptor changes in children.

Table A3.  The major correlation between variables (maternal age, birth weight) and cell surface receptor changes in children.

Table A4.  Total dendritic and macrophage- and dendritic-like cells in samples of blood from children in the Michalovce (n = 301) and Svidnik/Stropkov (n = 61) districts.

Table A5.  Total CD4⁺ T-cell subtypes in samples of blood from children in the Michalovce (n = 301) and Svidnik/Stropkov (n = 61) districts.

Table A6.  CD marker correlation between samples of blood from children in the total study cohort.