DISTINCT T-cell populations may provide new insight into disease activity and treatment response in children with eosinophilic oesophagitis (EoE), according to new research.
Single-cell profiling revealed greater immune-cell infiltration during active EoE, with T helper 2 (TH2) cells enriched during active disease and TH17 cells relatively depleted. Researchers also identified differences in residual T-cell infiltration between children treated with proton-pump inhibitors (PPI) and topical steroids.
EoE is a chronic immune- and antigen-mediated disease of the oesophagus characterised by eosinophil-predominant inflammation. Current assessment of disease activity relies heavily on eosinophil counts in oesophageal tissue.
However, eosinophil counts may not fully reflect disease activity or symptom resolution, while patients can continue to experience oesophageal changes and symptoms despite achieving histological remission. Other immune cells, including mast cells and T-cell subpopulations, may therefore play an important role.
Researchers investigated immune-cell infiltration throughout the disease course in children with EoE, focusing particularly on T-cell populations.
The study included 50 children with EoE, alongside 33 with gastro-oesophageal reflux disease and 67 with functional disorders. Researchers analysed 114 biopsies using multiparametric immunofluorescence and performed single-cell RNA sequencing on T cells from 82 biopsies, encompassing 35,112 cells.
Immune-cell infiltration was significantly higher in active EoE than in inactive disease and the control groups.
Single-cell analysis showed that TH2 cells and activated GNLY-positive CD8+ T cells were positively correlated with oesophageal eosinophilia. Conversely, IL-17-positive CD4+ T cells showed a negative correlation with eosinophilia.
TH2 cells were significantly enriched during active EoE. Overall, active disease was characterised by enrichment of TH2 cells, IL-10-high regulatory T cells, and cytotoxic CD8+ T cells, while TH17 cells were relatively depleted.
Researchers also observed differences in T-cell clonality. Absolute T-cell clone size was greater in active EoE than in inactive disease and controls, although diversity and the proportion of expanded clonotypes did not differ significantly.
Treatment type was also associated with differences in the immune landscape during remission.
CD8+ T-cell infiltration was significantly greater in children receiving PPI therapy compared with those treated with topical steroids. Overall, topical steroid treatment was associated with lower residual T-cell infiltration than PPI therapy.
The authors concluded that distinct immune profiles are associated with disease activity and treatment response in paediatric EoE. However, analysis of treatment-induced changes was limited by low T-cell yields in biopsies following topical steroid treatment.
The findings suggest that looking beyond eosinophil counts towards the wider immune environment, including specific T-cell populations, could provide a more detailed understanding of EoE activity and response to treatment.
Reference
Hoelz H et al. Single-Cell Profiling Links T-Cell Accumulation and TH2/TH17 Dynamics to Eosinophilic Esophagitis (EoE) Activity in Children. Allergy. 2026.
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