Nonspecific increase of αβTCR⁺ double-negative T cells in pediatric rheumatic diseases

An increased number of double-negative T (DNT) cells expressing the αβ T cell receptor (αβ⁺DNT cells) is one of the diagnostic criteria for autoimmune lymphoproliferative syndrome (ALPS). Moreover, these cells are expanded in a widely used murine model for lupus. However, the homeostasis of αβ⁺DNT cells remains inadequately investigated in rheumatic disorders, especially in pediatric patients.

In this cross-sectional, prospective, and observational study, children with rheumatic disorders and healthy controls were recruited to analyze the quantity and characteristics of circulating DNT cells using flow cytometry.

Overall, the two study groups did not differ in their total DNT cell pool in the bloodstream. However, the number of αβ⁺DNT cells was significantly higher in rheumatic children than that in the controls, whereas the γδ⁺DNT cells remained similar. This expansion in the circulating pool of αβ⁺DNT cells was comparable across different rheumatic diseases, all showing significant differences from the controls in this regard. Moreover, no significant correlation was found between αβ⁺DNT cell numbers and disease activity.

These preliminary results indicate that circulating αβ⁺DNT cells are significantly expanded in children with rheumatic disorders; however, this finding appears to be a nonspecific (disease-unrelated) marker of autoimmunity. Further and larger studies are necessary to better investigate and define the role of DNT cells in pediatric rheumatic diseases.