(211) Investigating the Regulation of T Cell Activation by Microplastics and Selected Perfluoroalkyl Substances via High-Dimensional Spectral Flow Cytometry

Introduction/Rationale: The accumulation of microplastics (MPs) and perfluoroalkyl substances (PFAS) in the environment poses a potential threat to human immune competence. While the toxicological profiles of these contaminants are being mapped, the temporal dynamics of their immunomodulatory effects—particularly under conditions of chronic exposure—remain unclear. This study aims to utilize high-dimensional profiling to elucidate how the duration of exposure (acute vs. chronic) influences the capacity of MPs and specific PFAS congeners to perturb T cell signaling, functional competence, and exhaustion phenotypes.

Methods: Human primary PBMCs were exposed to MPs and four PFAS congeners (PFHxA, PFOA, PFOS, PFNA) under short-term or 2-week chronic conditions. Following TCR stimulation, a 30-parameter Activation-Induced Marker (AIM) assay using spectral flow cytometry quantified activation, exhaustion, and cytokine profiles.

Results: MPs and PFAS exhibited distinct immunomodulatory effects depending on exposure duration. Acute exposure primarily altered early activation kinetics, with PFHxA and PFOA differentially regulating CD137 and CD154. Chronic exposure induced broader functional changes, including acquisition of exhaustion phenotypes, shifts in memory differentiation, and altered polyfunctional cytokine responses through pathways not observed in acute models.

Conclusion: MPs and PFAS regulate T cell immunity in a time-dependent manner, transitioning from short-term signaling perturbations to chronic functional reprogramming. These findings highlight specific windows where environmental contaminants may compromise long-term immune competence.