Prognostic factors for progression of visual field deterioration in patients with primary open-angle glaucoma

Abstract

Regulatory T cells (Tregs) play an important role in the maintenance of self-tolerance and immune homeostasis. Interleukin-2 (IL-2) is critical for Treg expansion, activity and survival. Previous studies have demonstrated that low-dose IL-2 resulted in the selective expansion of Tregs and the clinical improvement of auto-immune disease. To examine the mechanisms whereby IL-2 affects Treg apoptosis through the intrinsic pathway, we used BH3 profiling, and quantitated mitochondrial apoptotic priming. This pattern suggests that Tregs were more primed than conventional CD4 T cells (Tcons) in a BCL2-dependent manner. Tregs expressed lower levels of BCL2 than Tcons. To examine the functional effects of IL-2, sorted Tregs and Tcons were cultured with different concentrations of IL-2. Low-dose IL-2 (10 IU/mL) lowered priming and increased BCL2 expression in Tregs. However, higher concentrations of IL-2 (>100 IU/mL) were required to increase BCL2 expression and decrease priming in Tcons. Apoptosis assays also revealed that low-dose IL-2 reduced susceptibility to apoptosis only in Tregs. ABT-199, a selective BCL2 inhibitor, enhanced the priming and apoptosis of both Tcells. IL-2 reversed the effects of ABT-199 for Tregs only. This provides further evidence that the inhibition of intrinsic pathway apoptosis mediated by IL-2 in Tregs is dependent on BCL2

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