First they confirmed that there is in fact increased expression of Foxp3+ cells in the intestinal mucosa of untreated celiac patients; happily, they write that "no significant differences were noted in the number of Foxp3+ cells in biopsy samples of treated celiac disease in comparison with biopsy samples of non-celiac disease controls." Next, they used an in vitro gliadin challenge system - no celiac patients were harmed during the course of this study! - to see if the increase in this cell population was dependent on gliadin, and it was. T cells are so named because they are made in the thymus; this demonstration that they can originate in the small intestine lamina propria is interesting. Treg cells are generally immunosuppressive, and the Treg cells isolated from celiac guts demonstrated this immunosuppressive ability in vitro. So the researchers wondered: why is there still so much inflammation in untreated celiac disease patients? They found that the cytokine IL-15 could suppress the proliferation of Treg cells, and completely shut down their ability to produce interferon gamma (IFN- γ ). This is at least partially because Treg cells from celiac patients turn out to have a significantly higher surface density of receptors for IL-15 than Treg cells from healthy controls, rendering them more sensitive to IL-15's effects.
Zanzi et al bolstered their findings by achieving the same results using two independent experimental methods. It is not yet clear how IL-15 impairs the suppressive activity of Treg cells. But these scientists are actively working on it.