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Wang, S.-H. ; Zissler, U.M. ; Büttner, M. ; Heine, S. ; Heldner, A. ; Kotz, S.* ; Pechtold, L.* ; Kau, J.* ; Plaschke, M.* ; Ullmann, J.T. ; Guerth, F. ; Oelsner, M. ; Alessandrini, F. ; Blank, S. ; Chaker, A. ; Schmidt-Weber, C.B. ; Jakwerth, C.A.

An exhausted phenotype of TH2 cells is primed by allergen exposure, but not reinforced by allergen-specific immunotherapy.

Allergy 76, 2827-2839 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BACKGROUND: Studies show that proallergic TH 2-cells decrease after successful allergen-specific immunotherapy (AIT). It is likely that iatrogenic administration of allergens drives these cells to exhaustion due to chronic T cell receptor stimulation. This study aimed to investigate the exhaustion of T cells in connection with allergenexposure during AIT in mice and two independent patient cohorts. METHODS: OVA-sensitized C57BL/6J mice were challenged and treated with OVA, and the development of exhaustion inlocal and systemic TH 2-cells was analyzed.In patients, the expression of exhaustion-associated surface markers on TH 2-cells was evaluated using flow cytometry in a cross-sectional grass pollen allergy cohort with and without AIT.The treatment effect was further studied in PBMC collected from a prospective long-termAIT cohort. RESULTS: The exhaustion-associated surface markers CTLA-4 and PD-1 were significantly upregulated on TH 2-cells upon OVA aerosol exposure in OVA-allergic compared to non-allergic mice. CTLA-4 and PD-1decreased after AIT, in particular on the surface oflocal lung TH 2-cells. Similarly, CTLA-4 and PD-1 expression were enhanced on TH 2-cells from patients with allergic rhinitis with an even stronger effect in those with concomitant asthma. Using an unbiased Louvain clustering analysis, we discoveredalate-differentiated TH 2 population expressing both markers that decreased during up-dosing but persisted long-term during the maintenance phase. CONCLUSIONS: This study shows that allergen exposure promotes CTLA-4 and PD-1 expression onTH 2-cells, andthat the dynamic change in frequencies of exhausted TH 2-cells exhibits a differential pattern during the up-dosing versus the maintenance phases of AIT.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ait ; Ctla-4 ; Pd-1 ; T Cell Exhaustion ; Proallergic Th2; T-cells; Immune-responses; Pd-1; Effector; Asthma; Ctla-4; Differentiation; Inflammation; Persistence; Expression
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Journal Allergy
Quellenangaben Volume: 76, Issue: 9, Pages: 2827-2839 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Allergy Research (IAF)
Institute of Computational Biology (ICB)
Grants Helmholtz Inflammation Immunology
German Center for Lung Research (DZL)