Proteomics of T cell differentiation!

Scientists have carried out one of the most comprehensive studies into how immune cells sense and respond to their environment to fight infection and destroy tumors.

The research team published their findings in the journal Nature Immunology, said the results provide important insights into how immune responses might be manipulated for the treatment of autoimmune diseases and cancer.

The study was focused on T lymphocytes, a population of white blood cells essential for immune responses to cancer, bacteria and viruses, and transplanted organs.

They mapped how these cells control expression of more than 9,000 proteins as they take part in immune responses. They also mapped in fine detail how an important immune-suppressive drug, used to prevent organ rejection in transplants, selectively controls these processes.

The authors reveal that lymphocyte environment sensing is controlled by immune activation, and that CD4⁺ and CD8⁺ T cells differ in their intrinsic nutrient transport and biosynthetic capacity.

They also reveal shared and divergent outcomes of mTORC1 inhibition in naïve versus effector T cells: mTORC1 inhibition impaired cell cycle progression in activated naïve cells, but not effector cells, whereas metabolism was consistently impacted in both populations. 

One of the senior authors said, "These results have implications for our understanding of how harmful or beneficial immune responses can be manipulated for better health outcomes in organ transplantation and cancer.

"A critical discovery is that exposure to foreign stimuli, such as viruses and bacteria, make T lymphocytes switch on expression of key sensors for oxygen and nutrients and also make T lymphocytes switch on expression of transporters that allow cells to import nutrients from their environment.

"Drugs used to block immune responses work by controlling these key metabolic pathways."

The study also shows how the ability of immune cells to mount effective responses can be shaped by the oxygen and nutrient environment the cells work in.

The research team explored how T cells re-program expression of thousands of cellular proteins in response to stimulation and provided a comprehensive understanding of how immune-suppressive drugs control T lymphocyte behavior.

https://www.dundee.ac.uk/news/2019/from-sleeping-cell-to-assassin--how-immune-cells-work.php

https://www.nature.com/articles/s41590-019-0495-x