Hallmarks of T-cell Exit from Quiescence

The appropriate activation of the adaptive immune system relies upon the reprogramming of naïve T cells into specialized effector T cells that can combat pathogens and tumors. Naïve T cells are actively maintained in a state of hyporesponsiveness termed quiescence, which is characterized by small cell size, low proliferative rate, and low basal metabolism. Engagement of antigen and costimulatory receptors drives T cells to exit quiescence to promote subsequent clonal expansion and functional differentiation. The exit from quiescence, which precedes activation-induced proliferation, is associated with extensive remodeling of cellular morphology and metabolism. Here, we define and discuss the implications of the six key features of the exit of naïve T cells from quiescence: (i) cell-cycle entry, (ii) cell growth, (iii) autocrine or paracrine interleukin-2 signaling, (iv) anabolic metabolism, (v) nutrient uptake, and (vi) remodeling of mitochondrial function. Ultimately, understanding how naïve T cells meet each of these requirements for quiescence exit will allow for the tuning of T-cell responses to treat infectious diseases, autoimmunity, and cancer. Cancer Immunol Res; 6(5); 502-8. ©2018 AACR.