In utero per - and polyfluoroalkyl substances (PFAS) exposure and changes in infant T helper cell development among
Darline Castro Meléndez1, Nathan Laniewski2, Todd A Jusko3
1Department of Immunology, Microbiology and Virology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States.
Insights
Prenatal exposure to PFAS chemicals alters infant T-cell development, impacting immune responses. Higher PFAS levels were linked to changes in T-follicular helper and T-helper 2 cells by 12 months of age.
Area of Science:
- Immunology
- Environmental Health
- Developmental Biology
Background:
- Prenatal exposure to toxicants like PFAS can disrupt immune development.
- T-cells are crucial for orchestrating immune responses.
- Early life PFAS exposure effects on infant T-cell development are not well understood.
Purpose of the Study:
- To model longitudinal changes in CD4+ T-cell subpopulations from birth to 12 months.
- To investigate the association between in-utero PFAS exposure and infant T-cell development.
Main Methods:
- Maternal-infant dyads were recruited (n=200) and followed for one year.
- Maternal serum PFAS concentrations were measured during pregnancy.
- Infant lymphocyte frequencies were assessed using mass cytometry and analyzed with linear mixed-effects models.
Main Results:
- In-utero PFAS exposure correlated with changes in multiple infant CD4+ T-cell subpopulations.
- Significant associations were observed for T-follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months.
- Increased PFOS exposure was linked to lower Tfh and higher Th2 cell percentages.
Conclusions:
- Maternal PFAS exposure is associated with cell-specific alterations in the infant T-cell compartment.
- These changes may impact the development of well-regulated, protective immunity in children.
- Further research is needed to explore PFAS-associated T-cell distribution and adverse immune outcomes.
Background:
Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child's ability to generate a well-regulated, protective immune response. T-cells coordinate with all immune cell types to orchestrate both cellular and antibody-mediated responses. While there is compelling evidence that PFAS alters immunity in humans, the specific effects of early life PFAS exposure on infant T-cell development are unreported. Because of their central role in immunity, altered T-cell development in infants would have implications on immune responses broadly and long-term.
Objectives:
We seek to model longitudinal changes in the frequency of functionally distinct CD4+ T-cell subpopulations from birth through 12 months and their association with in-utero PFAS exposure.
Methods:
Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant's first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, PFHXS and PFDA) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n=200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and pre-pregnancy body mass index.
Results:
In-utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T-follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log2-unit increase in PFOS was associated with lower Tfh [0.17% (95%CI: -0.30, -0.40)] and greater Th2 [0.27% (95%CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, PFHXS and PFDA. TEXT.
Discussion:
Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated, protective immunity. Future studies into the role of PFAS-associated T-cell distribution and risk of adverse immune-related health outcomes in children are warranted. https://doi.org/10.1289/EHP16726.
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