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In adult X-CGD patients, regulatory T cells are expanded while activated T cells display a NOX2-independent ROS increase.

Immunology Letters 2024 Februrary 2
The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4+ T lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4+ T cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells.

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