Interstitial Migration of CD8αβ T Cells in the Small Intestine Is Dynamic and Is Dictated by Environmental Cues

Summary: The migratory capacity of adaptive CD8αβ T cells dictates their ability to locate target cells and exert cytotoxicity, which is the basis of immune surveillance for the containment of microbes and disease. The small intestine (SI) is the largest mucosal surface and is a primary site of pathogen entrance. Using two-photon laser scanning microscopy, we found that motility of antigen (Ag)-specific CD8αβ T cells in the SI is dynamic and varies with the environmental milieu. Pathogen-specific CD8αβ T cell movement differed throughout infection, becoming locally confined at memory. Motility was not dependent on CD103 but was influenced by micro-anatomical locations within the SI and by inflammation. CD8 T cells responding to self-protein were initially affected by the presence of self-Ag, but this was altered after complete tolerance induction. These studies identify multiple factors that affect CD8αβ T cell movement in the intestinal mucosa and show the adaptability of CD8αβ T cell motility. : Using in vivo imaging of pathogen- and self-specific CD8 T cells in the small intestine, Thompson et al. reveal dynamic changes in the speed and volume of tissue surveyed by CD8 T cells over time after antigen encounter. Migration was CD103 independent, and motility was most limited during the memory response. Keywords: resident memory T cells, tolerance, immune surveillance, T cell migration, motility, 2-photon microscopy, mucosal immunity, integrins, mathematical modeling, CD8 T cells