Dataset: Sequential induction of effector function, tissue migration and cell death during polyclonal activation of regulatory T-cells
The ability of Treg-cells to produce interleukin-10 (IL-10) is important for the limitation of inflammation at environmental interfaces...
The ability of Treg-cells to produce interleukin-10 (IL-10) is important for the limitation of inflammation at environmental interfaces like colon or lung. Under steady state conditions, however, only few Treg-cells produce IL-10 ex vivo. To investigate the origin and fate of IL-10 producing Tregcells we used a superagonistic mouse anti-mouse CD28 mAb (CD28SA) for polyclonal in vivo stimulation of Treg-cells, which not only led to numeric expansion but also to a dramatic increase in IL- 10 production. IL-10 secreting Treg-cells strongly upregulated surface receptors associated with suppressive function, and had higher but IL-10 independent, in vitro suppressive capacity than nonproducing Treg-cells. Furthermore, polyclonally expanding Treg-cells shifted their migration receptor pattern after activation from a lymph node-seeking to an inflammation-seeking phenotype, explaining the preferential recruitment of IL-10 producers to sites of ongoing immune responses. Finally, we observed that IL-10 producing Treg-cells from CD28SA stimulated mice were more apoptosis-prone in vitro than their IL-10 negative counterparts. These findings support a model where prolonged activation of Treg-cells results in terminal differentiation towards an IL-10 producing effector phenotype associated with a limited lifespan, implicating built-in termination of immunosuppression. total samples analysed are 4
- Dec.12, 2014
- Nov.12, 2014