@article{LangenhorstGogishviliRibechinietal.2012, author = {Langenhorst, Daniela and Gogishvili, Tea and Ribechini, Eliana and Kneitz, Susanne and McPherson, Kirsty and Lutz, Manfred B. and H{\"u}nig, Thomas}, title = {Sequential induction of effector function, tissue migration and cell death during polyclonal activation of mouse regulatory T-cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76009}, year = {2012}, abstract = {The ability of CD4+Foxp3+ regulatory T-cells (Treg) to produce interleukin (IL)-10 is important for the limitation of inflammation at environmental interfaces like colon or lung. Under steady state conditions, however, few Tregs produce IL-10 ex vivo. To investigate the origin and fate of IL-10 producing Tregs we used a superagonistic mouse anti-mouse CD28 mAb (CD28SA) for polyclonal in vivo stimulation of Tregs, which not only led to their numeric expansion but also to a dramatic increase in IL-10 production. IL-10 secreting Tregs strongly upregulated surface receptors associated with suppressive function as compared to non-producing Tregs. Furthermore, polyclonally expanding Tregs shifted their migration receptor pattern after activation from a CCR7+CCR52 lymph node-seeking to a CCR72CCR5+ inflammationseeking phenotype, explaining the preferential recruitment of IL-10 producers to sites of ongoing immune responses. Finally, we observed that IL-10 producing Tregs 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 Tregs results in terminal differentiation towards an IL-10 producing effector phenotype associated with a limited lifespan, implicating built-in termination of immunosuppression.}, subject = {Medizin}, language = {en} }