Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections.

CD8+ T cells represent one of the most versatile immune cells critical for clearing away viral infections. Due to their important role, CD8+ T cell activation and memory formation during viral infection have been the focus of several studies recently. Although CD8+ T cell activation and memory formation have been associated with metabolic alterations, the molecular understanding behind T cells choosing one type of metabolism over others based on their differentiation stage is still unclear. This review focuses on how the signaling molecules and cellular processes that are characteristic of CD8+ T cell activation and memory formation also play a critical role in selecting specific type of metabolism during viral infections. In addition, we will summarize the epigenetic factors regulating these metabolic alterations.

NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells.

Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8+ T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8+ T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.

Optimizing the production of suspension cells using the G-Rex "M" series.

Broader implementation of cell-based therapies has been hindered by the logistics associated with the expansion of clinically relevant cell numbers ex vivo. To overcome this limitation, Wilson Wolf Manufacturing developed the G-Rex, a cell culture flask with a gas-permeable membrane at the base that supports large media volumes without compromising gas exchange. Although this culture platform has recently gained traction with the scientific community due to its superior performance when compared with traditional culture systems, the limits of this technology have yet to be explored. In this study, we investigated multiple variables including optimal seeding density and media volume, as well as maximum cell output per unit of surface area. Additionally, we have identified a novel means of estimating culture growth kinetics. All of these parameters were subsequently integrated into a novel G-Rex "M" series, which can accommodate these optimal conditions. A multicenter study confirmed that this fully optimized cell culture system can reliably produce a 100-fold cell expansion in only 10 days using 1L of medium. The G-Rex M series is linearly scalable and adaptable as a closed system, allowing an easy translation of preclinical protocols into the good manufacturing practice.