Fig. 2.
Activation of regulatory T-cells. Regulatory T-cells are a subpopulation of immuno-modulatory T-cells characterized by expression of the cell surface molecules cluster of differentiation (CD)4 and CD25, and by the presence of the transcription factor forkhead box P3 (FoxP3). Binding of interleukin (IL)-2 to CD25 induces proliferation of regulatory T-cells and is required to ensure their physiologic maintenance.48 FoxP3 expression is induced under hypoxic conditions and regulates target genes that govern immuno-modulatory functions.49 Neuroprotective effects are mediated by regulatory augmentation of T-cell proliferation and activity as well as by synthesis of antiinflammatory cytokines such as IL-1039 and transforming growth factor (TGF)-β.37 Therapeutic activation of regulatory T-cells has been successfully achieved through exogenous administration of IL-2 in clinical trials of primarily nonneurologic diseases.51,52 This approach may serve as a model for studying neuroprotective effects of regulatory T-cells in perioperative stroke.