Single-cell characterization of dog allergen–specific T cells reveals TH2 heterogeneity in allergic individuals

Autor: Rytkönen-Nissinen Marja, Virtanen Tuomas, Vandamme Céline, Rauno J. Harvima, Kinnunen Tuure, Lönnberg Tapio, Randell Jukka
Rok vydání: 2022
Předmět:
Zdroj: Journal of Allergy and Clinical Immunology. 149:1732-1743.e15
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2021.11.018
Popis: Background Allergen-specific type 2 CD4+ T helper (Th2) cells are critically involved in the pathogenesis of IgE-mediated allergic diseases. However, the heterogeneity of the Th2 response has only recently been appreciated. Objective To characterize at the single-cell level the ex vivo phenotype, transcriptomic profile and TCR repertoire of circulating CD4+ T cells specific to the major dog allergens Can f 1, Can f 4 and Can f 5 in subjects with and without dog allergy. Methods Dog allergen-specific memory CD4+ T cells were detected ex vivo by flow cytometry using a CD154-based enrichment assay and single-cell sorted for targeted gene expression analysis and TCR sequencing. Results Dog-allergen-specific T-cell responses in allergic subjects were dominantly of Th2-type. Th2 cells could be phenotypically further divided into three subsets, which consisted of Th2-like (CCR6-CXCR3-CRTH2-), Th2 (CCR6-CXCR3-CRTH2+CD161-) and Th2A (CCR6-CXCR3-CRTH2+CD161+CD27-) cells. All these subsets were non-existent within the allergen-specific T-cell repertoire of healthy subjects. Single-cell transcriptomic profiling confirmed the Th2-biased signature in allergen-specific T cells from allergic subjects and revealed a Th1/17 signature in nonallergic subjects. TCR repertoire analyses showed that dog allergen-specific T cells were diverse and allergic subjects demonstrated less clonality compared to non-allergic donors. Finally, TCR and transcriptomic analyses revealed a close relationship between Th2-like, Th2 and Th2A cells, the last ones representing the most terminally differentiated and highly polarized subtype. Conclusions Our study demonstrates heterogeneity within allergen-specific Th2 cells at the single-cell level. The results may be utilized for improving immune monitoring after allergen immunotherapy and for designing targeted immunomodulatory approaches.
Databáze: OpenAIRE
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