AUTHOR=Seyfarth Julia , Mütze Nathalie , Antony Cruz Jennifer , Kummer Sebastian , Reinauer Christina , Mayatepek Ertan , Meissner Thomas , Jacobsen Marc 

TITLE=CD4+ T-Cells With High Common γ Chain Expression and Disturbed Cytokine Production Are Enriched in Children With Type-1 Diabetes

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00820

DOI=10.3389/fimmu.2019.00820

ISSN=1664-3224

ABSTRACT=<p>The common gamma chain (γ<sub>c</sub>) contributes to the formation of different cytokine receptors [e.g., IL-2 receptor (IL-2R), IL-7R, and IL-15R], which are important for generation of self-reactive T-cells in autoimmune diseases, like in type 1 diabetes (T1D). Whereas, the roles of membrane and soluble IL-2Rα and IL-7Rα variants in T1D disease pathogenesis are well-described, effects of γ<sub>c</sub> expression and availability for dependent receptors remain elusive. We investigated expression of the γ<sub>c</sub> and dependent receptors on T-cells and soluble γ<sub>c</sub> concentrations in serum from patients with T1D (<italic>n</italic> = 34) and healthy controls (<italic>n</italic> = 27). Effector T-cell cytokines as well as IL-2, IL-7, and IL-15 induced STAT5 phosphorylation were analyzed to determine functional implications of differential γ<sub>c</sub> expression of CD4<sup>+</sup> T-cell subsets classified by t-distributed Stochastic Neighbor Embedding (t-SNE) analyses. We found increased γ<sub>c</sub> and IL-7Rα expression of CD4<sup>+</sup> T-cells from T1D patients as compared to controls. t-SNE analyses assigned differential expression to subsets of memory T-cells co-expressing γ<sub>c</sub> and IL-7Rα. Whereas, γ<sub>c</sub> expression was positively correlated with IL-2Rα in memory T-cells from healthy controls, no dependency was found for patients with T1D. Similarly, the effector T-cell cytokine, IL-21, correlated inversely with γ<sub>c</sub> expression in healthy controls, but not in T1D patients. Finally, T1D patients with high γ<sub>c</sub> expression had increased proportions of IL-2 sensitive pSTAT5<sup>+</sup> effector T-cells. These results indicated aberrantly high γ<sub>c</sub> expression of T-cells from T1D patients with implications on dependent cytokine receptor signaling and effector T-cell cytokine production.</p>