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Mass cytometry-based identification of a unique T-cell signature predicting childhood AA
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  • Hartmann Raifer,
  • Axel Schulz,
  • Johanna Theodorou,
  • Addi Romero,
  • Andreas Böck,
  • Wilhelm Bertrams,
  • Bernd Schmeck,
  • Michael Lohoff,
  • Hyun-Dong Chang,
  • Bianca Schaub,
  • Henrik Mei,
  • Magdalena Huber
Hartmann Raifer
Philipps University Marburg

Corresponding Author:[email protected]

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Axel Schulz
Deutsches Rheuma-Forschungszentrum Berlin
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Johanna Theodorou
Dr. von Hauner Children´s Hospital, University Hospital, LMU Munich
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Addi Romero
University of Marburg
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Andreas Böck
University Children's Hospital, Kubus Research Centre
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Wilhelm Bertrams
University of Marburg
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Bernd Schmeck
University of Marburg
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Michael Lohoff
University of Marburg
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Hyun-Dong Chang
Deutsches Rheuma-Forschungszentrum Berlin
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Bianca Schaub
University Childrens Hospital
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Henrik Mei
Deutsches Rheuma-Forschungszentrum Berlin
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Magdalena Huber
University of Marburg
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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.