"Nature Immunology" clarifies the mystery of why T cells "deplete"

Researchers at the Perelman School of Medicine at the University of Pennsylvania have revealed an important limitation of the immune system in the long-term fight against cancer or viruses: T cells are one of the most powerful weapons in the immune system of humans and other vertebrates.

Scientists already know that when T cells are exposed to these enemies for a long time, they lose their ability to fight viruses and tumors

"Our results show that once T cells are depleted, they are basically still in a depleted state, so it is difficult to make them effective virus and cancer resisters again," Perelman Medical University of Pennsylvania (University of Pennsylvania) Said Dr.

The understanding of the problem of T cell failure appeared in the study of long-term viral infections about 20 years ago, including research by Whitley and his laboratory

Researchers hope that by blocking certain activity on depleted T cells and inhibiting receptors, they can rejuvenate T cells in cancer patients and patients who have been infected with HIV or hepatitis C virus for a long time

An unresolved question is whether depleted T cells can be restored to normal function and to what extent if they are no longer exposed to the virus or tumor that depleted them

Wherry and his colleagues, including first author Mohamed Abdel-Hakeem, a postdoctoral assistant researcher in the Wherry lab, solved this problem in a new study

The researchers found that most depleted T cells died when they were no longer exposed to LCMV

A cell is programmed to be in a certain state or identity by an "epigenetic" molecular system that controls which genes in the cell are active or inactive

Fatigue obviously leaves long-lasting "epigenetic scars" in T cells, limiting their ability to support the immune response

In principle, treatments that reverse these epigenetic changes can convert the depleted T cells in the patient's body into normal memory T cells again