Mass cytometry-based identification of a unique T-cell signature
predicting childhood AA
Abstract
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.