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

Immunol Lett. 2024 Apr:266:106839. doi: 10.1016/j.imlet.2024.106839. Epub 2024 Feb 1.


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.

Keywords: NADPH-oxidase; Regulatory T cells; TNFR2; X-CGD.

MeSH terms

  • Adult
  • Granulomatous Disease, Chronic* / genetics
  • Granulomatous Disease, Chronic* / metabolism
  • Humans
  • Mutation
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Reactive Oxygen Species / metabolism
  • T-Lymphocytes, Regulatory


  • NADPH Oxidases
  • Reactive Oxygen Species