T cells are the soldiers of the immune system, always ready to respond to threats ranging from pathogenic microbes to tumors. Among them, CD8+ T cells are the main effector cells within the immune system used to eliminate infectious pathogenic microbial infections and tumor cells.
A new study by Chen Lieping\'s team shows that T cells that are not rested and maintained may die quickly and cause individuals to be more susceptible to pathogens. The study, titled "The CD8α-PILRα interaction maintains CD8+ T cell quiescence", was published in the leading international academic journal Science on May 26, 2022.
This study shows that CD8α is essential for maintaining CD8+ T cells in a resting state in peripheral lymphoid organs. Deletion of CD8α causes spontaneous activation of naive CD8+ T cells and memory CD8+ T cells from a resting state and subsequent death in the absence of exposure to specific antigens. This study also identified PILRα as a ligand for CD8α, and disruption of CD8α-PILRα interactions was able to break the resting state of CD8+ T cells.
In the absence of antigen exposure, CD8α-PILRα interactions actively maintain the resting state of the peripheral T cell pool and CD8+ T cells. This also suggests that the resting state of CD8+ T cells maintained by CD8α-PILRα is required and that a lack of this maintenance of the resting state leads to their death.
In addition to acting as a T cell lineage marker, CD8 heterodimers also act as co-receptors to enhance T cell receptor (TCR) signaling following antigen stimulation. Whether CD8 performs other antigen-non-dependent functions is unknown.
T cells remain in a relatively quiescent resting state until the threat of pathogens or tumor cells is detected. However, the molecular mechanisms that allow T cells to maintain this inactive resting state remain unknown.
In this latest study, Chen Lieping\'s team at Yale University discovered that a protein called CD8α is present in CD8+ T cells, a subpopulation of T cells, and that its presence is essential for keeping CD8+ T cells in a resting state, which are the primary effector cells within the immune system used to eliminate infectious pathogenic microbial infections and tumor cells.
The team constructed conditional knockout CD8α mouse models in which CD8α was absent from peripheral CD8+ T cells, but did not affect normal thymus development. The results showed that the absence of CD8α prevented these protective CD8+ T cells from entering a resting state and caused them to die quickly, leaving the mice vulnerable to infection.
CD8a maintained the resting state of memory CD8+ T cells, as well as peripheral CD127 and CD122 expression. The team further identified the PILRα protein as a ligand for CD8α, and disruption of the CD8α-PILRα interaction resulted in the inability of memory CD8+ T cells and naive CD8+ T cells to maintain a resting state and led to their death.
As people age, they tend to lose naïve T cells and memory T cells, which makes older people more susceptible to infections. And the inability of T cells to remain resting may lead to greater susceptibility to infections and cancer.