Researchers from St. Jude Children’s Research Hospital revealed that the protein complex mTORC1 responds to cues from in and around developing T cells to influence whether the cells become conventional or unconventional T cells.
The protein complex mTORC1 primarily regulates cell growth and metabolism. The research led by Hongbo Chi, Ph.D., a St. Jude immunologists found that mTORC1 responds to cues from in and around developing T cells and intersects with metabolic activity. This behavior decides whether the cells become conventional or unconventional T cells. Moreover, researchers found that disrupting mTORC1 favored development of unconventional T cells at the expense of conventional T cells. Both the conventional and unconventional cells express different cell surface receptors and function differently. Understanding the mechanism of their fate is expected to harness the immune system to fight cancer, tame autoimmune diseases and combat infectious diseases. T cells play a vital role in the adaptive immune system to find and eliminate specific viruses and other threats. T cell are formed in the thymus after immature bone marrow cells travel there to mature and specialize. Specialty of T cells is partly evident by T cell receptors (TCRs) or antigen receptors. T cells rely on the T cell receptors to recognize targets and respond to changing conditions.
The team experimented with mice models and it was observed that activation of mTORC1 accelerates energy production through glycolysis and oxidation. This promotes anabolic metabolism, which in turn develops conventional αβ T cells. However, metabolism was disrupted when researchers disabled mTORC1. It resulted in reduction of conventional αβ T cells and increase of unconventional γδ T cells. Deleting a protein called RAPTOR in mTORC1 halted the functioning of mTORC1 and altered the metabolic balance in developing T cells, which enhanced formation of γδ T cells in the thymus and restrained αβ T cells. This eventually led to reduced anabolic metabolism with increased levels of toxic molecules called reactive oxygen species (ROS) and enhanced activity along a molecular pathway that promotes cell growth. The research was published in the journal Science Immunology on June 06, 2018.