The ectonucleotidase CD39 ultimately generates extracellular adenosine, modulating paracrine purinergic signaling. Here the authors show that IFNγ induction in CD8+ T cells is accompanied by NADH oxidase-dependent CD39 expression, which then inhibits IFNγ production in CD39-CD8+ T cells.
Interferon gamma (IFNγ)-producing CD8+ T cells (Tc1) play important roles in immunological disease.
Researchers report in the journal Nature Communications that CD3/CD28-mediated stimulation of CD8+ T cells to generate Tc1 cells, not only increases IFNγ production but also boosts the generation of reactive oxygen species (ROS) and augments expression of CD39.
Inhibition of NADPH oxidases or knockdown of gp91phox in CD8+ T cells abrogates ROS generation, which in turn modulates JNK and NFκB signalling with decreases in both IFNγ levels and CD39 expression.
CD39+CD8+ T cells substantially inhibit IFNγ production by CD39−CD8+ T cells via the paracrine generation of adenosine, which is operational via adenosine type 2A receptors. Increases in numbers of CD39+CD8+ T cells and associated enhancements in ROS signal transduction are noted in cells from patients with Crohn’s disease.
These findings provide insights into Tc1-mediated IFNγ responses and ROS generation and link these pathways to CD39/adenosine-mediated effects in immunological disease.