Background: Allergic asthma (AA) in childhood is characterized by a dominance of type 2 immunity and inefficient counter-regulation by type 1 immunity and/or Tregs among other mechanisms. However, a detailed analysis of T cells associated with paediatric AA is still needed. Methods: High-dimensional mass cytometry, algorithmic analysis and manual gating were applied to define the peripheral T-cell signature in treatment-naïve childhood AA. Results: The analysis revealed a changed T-cell profile in children with AA in comparison to healthy controls (HC) consisting of: (i) a lower frequency of memory CD8+ T cells, (ii) an overrepresentation of TIGIT+ICOS+ Th2 cells connected to a more symptomatic disease with allergic comorbidity and eosinophilia, and (iii) an altered Treg compartment. Within Tregs, the naïve/resting fraction was enriched in children with AA vs HC, it associated inversely with memory CD8+ T cells, and was linked to a lung function decline. Moreover, the ratio of TIGIT+ICOS+ Th2 cells to dysbalanced effector (e)Treg clusters significantly associated with eosinophilia. Thus, dysregulated Treg fractions were linked to a lung function and, on the other hand, to eosinophilia via TIGIT+ICOS+Th2 cells. The association of altered Treg clusters with the AA phenotype in ROC analysis underscored the importance of changes in the Treg compartment. Conclusions: Our approach identifies a unique T-cell signature of childhood AA and provides insights for pathophysiological involvement of dysbalanced Tregs, TIGIT+ICOS+ Th2 cells and CD8+ T memory cells. This can be useful for immunomonitoring, immunomodulation and for further studies in childhood AA.
