Huang Bo’s team Metabolically Analyzed T-cell Memory Formation and Maintenance


Huang Bo’s team, from the Institute of Basic Medical Sciences found that gluconeogenesis - glycogen metabolism - pentose phosphate is the key mechanism of CD8+T cell memory formation and maintenance. Relevant findings were published online in a paper entitled “A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells” on December 11 on Nature Cell Biology.

Activated CD8+ T cells efficiently kill virus-infected cells and tumor cells. After the killing, very few T cells survive and transform themselves into memory T cells so that these memory T cells can remove the same virus or tumor cells when re-encountering these virus or tumor cells, thus playing an essential role in the anti-tumor and anti-infective immunity processes of the organisms. It is of great theoretical and clinical significance to elucidate the mechanism of CD8+ T cell memory formation and maintenance though it is still a mystery to be solved. While studying the IL-15 induced in vivo CD8+ memory T cell model and the adoptive OT-1 T cell in vitro model from Lm-OVA-infected mice, Professor Huang Bo’s team found that CD8+ memory T cells utilize a unique glucose metabolism to form and retain memory. Glucose catabolism (glycolysis) is the basis for cells to gain energy. In contrast, glucose synthesis (gluconeogenesis) is the fundamental pathway for the organism’s nerve cells and red blood cells to gain energy. Gluconeogenesis is thought to be mainly present in hepatocytes. However, this study found that gluconeogenesis is very active in memory T cells. CD8 + memory T cells highly express the cytosolic phosphoenolpyruvate carboxykinase (PCK1), a key rate-limiting enzyme in gluconeogenesis, and catalyze oxaloacetate generating toward the 6-phosphoglucose. However, the 6-phosphoglucose is converted into glycogen instead of glucose. Synthetic glycogen decomposes and then generates 6-phosphate glucose, and this time the 6-phosphate glucose moves into the pentose phosphate pathway, resulting in reduced NADPH, to maintain high levels of reduced glutathione, timely remove intracellular free radical, so as to maintain the long-term survival of memory T cells. This unique mechanism is of important theoretical implications for the mass preparation of tumor-specific T-cells with memory phenotypes for reinfusion to treat tumor-bearing patients.


This research is sponsored by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-007) and National Natural Science Foundation of China. Professor Cao Xuetao from the Institute of Basic Medical Sciences and Professor Qin Xiaofeng from the Suzhou Institute of Systems Medicine participated in the study.




(Institute of Basic Medical Sciences)