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. 2023 Mar 1;133(5):e161593. doi: 10.1172/JCI161593

Figure 3. Different T cell reactivity pattern against A. fumigatus in pwCF.

Figure 3

(A) Ex vivo cytokine production of A. fumigatus–reactive CD154+ Tmem cells from healthy donors (IFN-γ, n = 158; IL-17A, n = 158; IL-4, n = 134; IL-10, n = 87) and pwCF (n = 200). (B) Representative dot plots for ex vivo cytokine staining of A. fumigatus–stimulated cells following ARTE. The percentage of cytokine-producing cells within CD154+ Tmem cells is indicated. (C) Direct comparison of A. fumigatus–reactive cytokine production for healthy donors (n = 134) and pwCF (n = 200). Cut-off values for cytokine-producing cells within CD154+ Tmem cells were determined by ROC analysis (see Supplemental Figure 2). Donors whose cell percentages exceeded the cut-off are color coded (yellow: IFN-γ ≥29%; light green: IL-17A ≥6.1%; light blue: IL-4lo ≥6.9%; dark blue: IL-4hi ≥12.9%. (D) Frequencies of A. fumigatus–reactive Tmem cells, as well as total and specific IgE levels for pwCF within the different A. fumigatus–specific T cell reactivity groups. (E) Representative plots depicting the stability of the different A. fumigatus–specific cytokine reactivity patterns. A. fumigatus–reactive T cells of pwCF were monitored at least 4 times over a period of up to 4 years. Relative expression of IFN-γ, IL-17A, and IL-4 within the CD154+ Tmem population is shown. (F) Distribution of the different A. fumigatus–specific cytokine reactivity patterns for healthy donors and pwCF. The percentages of donors in each group are indicated. (G) Incidence of ABPA in the different A. fumigatus–specific T cell reactivity groups. The percentages indicate patients with acute ABPA, a history of ABPA, or who never had ABPA at the time the measurement was done. (H) Heatmap depicting the correlation of the different A. fumigatus–reactive T cell groups with clinical parameters. Values were z score normalized for each parameter and are plotted as the mean value for each T cell reactivity group. Each symbol in A, C, and D represents 1 donor; horizontal lines indicate the mean in A. Truncated violin plots with quartiles and range are shown in D. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001, by 2-tailed Mann-Whitney U test (A) and Kruskal-Wallis test with Dunn’s post hoc test (D).