Phenotype of CD39/CD73 expressed on T cells in a mouse model of IPEX syndrome

Abstract

The combination of CD39 and CD73 degrade ATP to adenosine that shifts ATP-driven pro-inflammatory immune cell activity toward an anti-inflammatory state. This immunological switch is a major mechanism for regulatory T cells (Tregs) to control inflammation. However, in Treg-deficiency-induced autoimmune pathologies, exemplified by IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, with X-linked inheritance, as modeled by the scurfy (SF) mouse), the expression of these molecules on T cells is unknown. We analyzed homeostatic markers CD39 and CD73 on T cells in spleen and peripheral blood by flow cytometry in SF males and their sibling WT male mice at d21. Among Foxp3+ Tregs in WT mice, ~68% cells had CD39 and 85% cells had CD73 expression. In the spleens of SF mice, the % of CD39+CD4+ T cells was higher than the % in WT mice, while no difference was observed in the CD73+CD4+ T cells. In addition, the data showed ~70% of NonTregs expressed CD39, 2-fold higher than both % of CD73+ NonTregs in SF, and % of CD39+ NonTregs in WT. Only ~10% of these CD39+ and CD73+ NonTregs had the CD25 expression. The proportion of CD8+ T cells in splenocytes and blood of SF mice were significantly higher than those in WT mice. Amongst CD8+ T cells, the % of CD39+ T cells was significantly increased, conversely, the % of CD73+ T cells was significantly decreased in SF compared to WT mice. We conclude that normally, CD73 is a more highly expressed Treg surface marker than CD39; however, in Treg-deficiency, there is a higher expression by CD4+ T and CD8+ T cells of CD39 than CD73; and CD39 and CD73 expression may not be due to cell activation. This study provides data to aid further discovery of potential biomarkers and therapeutic targets in Treg deficiency diseases. Supported by grants from NIH/NIAID (R03AI153725)