JUL 09, 2018 7:00 PM PDT

Protein Complex Determines the Fate of T cells

WRITTEN BY: Caitlin Williams

T lymphocytes, or T cells, are a type of white blood cell essential to the immune system. These cells are part of the adaptive immune response and serve as trained guards for the body, finding and eliminating threats such as viruses and harmful bacteria.

T cells develop from precursor cells that travel from the bone marrow to the thymus where they mature and specialize. The cells undergo a series of differentiations and eventually split in to two distinct lineages, alpha beta and gamma delta, based on the protein chains on the cell. Alpha beta cells are considered conventional T cells, they circulate throughout the body and reside in the spleen and lymph nodes. Gamma delta cells are considered unconventional, found in smaller numbers, and reside in the gut, skin and other barrier tissues. Dr. Hongbo Chi of St. Jude’s Immunology Department said “We know that conventional and unconventional T cells are fundamentally different, they express different cell surface receptors. The cells have different functions. But until now the mechanism that helps decide their fates has remained largely unknown.”

While previous studies have focused on the effects of certain proteins like NOTCH and interleukin-7 on cell survival and growth, no studies have found a specific link between metabolic signals and lineage decisions or the interplay of metabolism with immune signals. Emerging studies have shown the involvement of rapamycin (mTOR) in integrating metabolic cues and immune signals to orchestrate T cell function and fate. But the role of mTOR signaling in T cell lineage fate between alpha beta and gamma delta has yet to be elucidated, until recently. 

A study from St. Jude’s Department of Immunology has shed some light on the mechanism behind T cell differentiation to alpha beta or gamma delta. Dr. Chi and his colleagues utilized genetically engineered mouse models to further elucidate the role of a protein complex, mTORC1, and its role in the fate of T cells.

Activation of this protein complex increased energy production via anabolic metabolism leading to increased development of alpha beta T cells. On the flip side, the mTORC1 complex was disabled by genetic deletion of the protein RAPTOR that is involved in the complex. This resulted in metabolism disruption, which resulted in an increase in gamma delta cells and a decrease in alpha beta cells. This deletion not only resulted in reduced anabolic metabolism but increased the level of reactive oxygen species (ROS), which is toxic to cells, and promoted cell growth by upregulating certain molecular pathways. This study showed that mTORC1 integrates both metabolic and signaling activity to dictate the fate of T-cell lineage and control ROS production as a key signal in this process.

"This research establishes mTORC1-driven metabolic signaling as a decisive factor in determining the fate of developing T cells and suggests metabolic processes are a fundamental mechanism that connects external signals with internal processes to guide the fate of immune cells," Chi said.

To read this study click here. To learn more about T cells and their role in the adaptive immune response watch the video below.

 

About the Author
Doctorate
Caitlin holds a doctorate degree in Microbiology from the University of Georgia where she studied Mycoplasma pneumoniae and its glycan receptors. She received her Bachelor's in Biology from Virginia Tech (GO HOKIES!). She has a passion for science communication and STEM education with a goal to improve science literacy. She enjoys topics related to human health, with a particular soft spot for pathogens.
You May Also Like
AUG 16, 2022
Health & Medicine
In Transplant Breakthrough, the Blood Type of a Donor Kidney is Changed
AUG 16, 2022
In Transplant Breakthrough, the Blood Type of a Donor Kidney is Changed
Blood types have to be considered when a person is receiving a kidney transplant. An individual with type A blood, for e ...
OCT 23, 2022
Immunology
The Double-Edged Sword of Iron Deficiency
OCT 23, 2022
The Double-Edged Sword of Iron Deficiency
Iron is a crucial nutrient. Most of the iron in the body is contained in red blood cells, as part of hemoglobin, which i ...
OCT 13, 2022
Health & Medicine
For the First Time Since 1979, Polio is Circulating in the United States
OCT 13, 2022
For the First Time Since 1979, Polio is Circulating in the United States
In light of a polio outbreak in Rockland County, New York, the United States has been added to the list of countries whe ...
OCT 19, 2022
Health & Medicine
New Guidance for Scheduling Your Mammogram and Covid-19 Booster
OCT 19, 2022
New Guidance for Scheduling Your Mammogram and Covid-19 Booster
New guidance from public health agencies recommends that screening mammograms be scheduled and attended regardless of va ...
OCT 21, 2022
Drug Discovery & Development
Developing an intranasal vaccine for gonorrhea
OCT 21, 2022
Developing an intranasal vaccine for gonorrhea
Gonorrhea is a common sexually transmitted disease that is caused by the bacteria Neisseria gonorrhoeae (N. gonorrhoeae) ...
NOV 07, 2022
Immunology
A High-Fat Diet May Alter Immunity
NOV 07, 2022
A High-Fat Diet May Alter Immunity
The physiological impact of various diets has been hotly debated for years. Scientists have now used a mouse model to sh ...
Loading Comments...