Chemokines: Critical Regulators of Memory T Cell Development, Maintenance, and Function.

Memory T cells are central to orchestrating antigen-specific recall responses in vivo. Compared to naïve T cells, memory T cells respond more quickly to cognate peptide:MHC with a shorter lag time for entering the cell cycle and exerting effector functions. However, it is now well established that this enhanced responsiveness is not the only mechanism whereby memory T cells are better equipped than naïve T cells to rapidly and robustly induce inflammation. In contrast to naïve T cells, memory T cells are composed of distinct subsets with unique trafficking patterns and localizations. Tissue-resident memory T cells persist in previously inflamed tissue and function as first responders to cognate antigen reexposure. In addition, a heterogeneous group of circulating memory T cells augment inflammation by either rapidly migrating to inflamed tissue or responding to cognate antigen within secondary lymphoid organs and producing additional effector T cells. Defining the mechanisms regulating T cell positioning and trafficking and how this influences the development, maintenance, and function of memory T cell subsets is essential to improving vaccine design as well as treatment of immune-mediated diseases. In this chapter, we will review our current knowledge of how chemokines, critical regulators of cell positioning and migration, govern memory T cell biology in vivo. In addition, we discuss areas of uncertainty and future directions for further delineating how T cell localization influences memory T cell biology.