Dynamics of antigen-specific T effector and T regulatory cell responses during pollen allergy season

Abstract

Chronic exposure to pollen is known to increase the amount circulating specific effector T cells (Teffs). However, little is known about the dynamic of specific regulatory T cell (Treg) responses during natural pollen exposure. Fresh blood samples from 8 alder allergic individuals and 6 grass allergic individuals were obtained before and during pollen season. Non allergic subjects were used as control. The magnitude and quality of pollen-specific Teff and Treg responses was determined ex vivo by flow cytometry using both CD154 and CD137 upregulation assay, respectively. Single cell RNAseq technology was used to assess the clonal expansion and TCR repertoires of both antigen-specific Teffs and Tregs, as well as stark differences in gene expression. Consistent with increased allergy symptoms, we observed a significant increase in T effector cell responses during pollen season with no significant chances in T cell phenotype. Following pollen exposure, multidimensional analysis was used to observe the induction of a subset of CD27+ T cells derived from the naïve compartment, providing rationale to the persistence of seasonal allergic disease. Strikingly, the frequency of allergen-specific Tregs decreased significantly after natural allergen exposure despite significantly increased activation (Ki67, PD-1, CD69). Finally, using single cell RNAseq technology, we are also able to show that allergic Teffs and Tregs in season share expanded, yet distinctly separate T cell repertoires. Exposure to seasonal allergens decreases antigen-specific regulatory T cell frequency, but induces activation and migration to exposed tissues. These activated Tregs have distinct TCR repertoires from effector populations.