A comparison of IL-5 and IL-10-producing antigen-specific clonal T cell repertoires

Abstract

Abstract Allergic rhinitis affects up to 40% of North Americans, and is associated with potentially debilitating symptoms. Allergen-specific immunotherapy (AIT) is a disease-modifying treatment associated with Treg induction and elevated IL-10 production. To date, it is unknown if IL-10-producing T cells are induced de novo or if AIT modulates allergen-specific Th2 cells to become tolerogenic. To investigate whether IL-5 and IL-10-producing antigen-specific T cells share a common T cell repertoire, we performed a longitudinal TCRβ sequence analysis of Timothy grass (TG)-specific T cells from donors who received AIT for 15 months. As a control, TCRβ sequencing was also performed on TG-specific T cells from an allergic donor. TG-specific cells were expanded by 14-day in vitro culture with a pool of immuno-dominant TG-derived T cells epitopes (TG pool). A pertussis epitope pool was used in parallel as a control. Subsequently, cells were restimulated with the same pool and allergen-specific cells were isolated by cytokine capture with column enrichment, sorting IL-5 and IL-10 -producing cells. The TCRβ repertoire was sequence from DNA isolated from sorted cells. Preliminary results revealed that in the TG pool-specific cells, some clonal overlap was observed between IL-10+ and IL-5+ cells, suggesting that a fraction of IL-10+ cells may originate from IL-5+ cells, but some are generated de novo. Longitudinal analysis of the allergen-specific TCR repertoire is a reliable method to determine if tolerogenic T cells are induced de novo or if they are modulated T cells that originate from the same repertoire as allergen-specific Th2 cells.